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Drug Delivery Systems and Targeting Explained | Drug Discovery & DDS

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TECHNOLOGY EXPLAINER

Drug Delivery Systems (DDS) and Targeting
— Understanding the limits of targeted delivery through the 0.7% rule

DDS (Drug Delivery System)Time requiredTechnology to deliver However, in the analysis of animal experiments of nanoparticles for cancer for 10 years,The amount delivered to solid tumor is 0.7% of the median doseComment If the product is still approved and the contents are seen in mass,The most part is the material of the transport side, such as lipids, polymers and albumin.Comment

Composition: FDA approved attachments (DailyMed), Drugs@FDA, FDA product guidance, review papers (Cancer Research/Nature Reviews Materials/Nature Communications/Nature Materials/Journal of Controlled Release etc.) as primary information / last updated September 2026

A small translucent ball drifts in a dark space, and an abstract concept image that only a part of it gathers near a light area
Concept diagram (AI generation image).It is expressed as an atmosphere of the situation that "there is a part of reaching the target place even if you send a lot".It does not indicate actual particle, organization, microscope image or product.
Composition of this article
  1. What is DDS?
  2. Four types of nano carriers: liposome, albumin particles, polymer micelles, polymer bonds
  3. Passive Targeting and EPR Effects – 1986 Report
  4. Debate on EPR Effects: What Does Not Effective in Humans?
  5. 0.7%
  6. Material Technician Perspective 1: Deciding 99% of the rest is “surface”
  7. Actively targeting and liganding – not the amount to be collected, the way to enter
  8. In small s, active targeting is a product
  9. Emission control - E tion is determined
  10. What is the weight of the drug?
  11. Material Technician Perspective 2: Read 17 years of later products from the FDA guidelines
  12. Issues and Undetermined
  13. Glossary/Reference Materials/Reference Table
Terms of Use

Facts= Contents described in the publication material (with link)
This paper's description of= The value calculated based on the specified premise
Undetermined / Future= Items that have not been confirmed as a plan, goal, and research stage
In addition to this, it is possible to organize structures and read materials and process designs."Description"is distinguished.

Medical care

About this articleExplanation of material technology and preparation technologyComment It does not evaluate and compare the effects and safety of individual medicines, but it is not medical advice. The composition and approval date of the product is quoted only the FDA attachments and those listed in Drugs@FDA. The results of animal experiments are not applicable to humans.

1. What is DDS?

  • What to do:without changing the drug itself,Wrapping, Bonding, EmbedIt is a technology that changes the destination in the body and the speed released (。 by this article). This series is a different axis from the type of medicine used in the drug discovery modalities.Technology of "carrying" that can be to any type of medicineHome
  • What materials are used:Duncan Nanosize (5-100 nm)"Polymer Theics"andPolymers - Drug bindings, polymers - protein bindings, polymer micells that share drugs, polyplexes for DNA deliveryInclude and organizeFactsHome This adds liposome and albumin particles
  • What’s hard:It is a very small part to reach the target location. Wilhelm et al., as a result of the past 10 years"Reached to solid tumors of nanoparticles received is only 0.7% at the center value"ReportFacts
The best line in this article

As you can imagine from the word "targeting", nanoparticles do not gather at the target place. Even with active targeting (rigund ), the amount of the tumor is almost unchanged,Changes: “cells or not in cells”There is a report of animal experiment that was —FactsHome On the other hand, if you see the contents of the approved product in mass,2 to 9 times of the drugThis paper's description of。 The performance of the DDS is large in material design and manufacturing of the transport side, not drugsThat is This article explains.

2. Four types of nano-carrier: liposom, albumin particles, polymer micelles, polymer bonds

There are a number of different types of structures in the "in " (nano carrier) that carries the drug. Rosenblum et al al al al al al al al al al al al US Doxil, Abraxane, Marqibo, DaunoXome, Onivyde, European Myocet, Mepact, Korean xol-PM, Japanese SMANCSHomeFacts。

4 types of nano-carrier (conception diagram) Red = drug / blue, green, tea = material of transport side 1 Liposome 2μm particles 3 Polymeric Micelle 4 Polymer binding Lipid Double Membrane Pouches Medicine in the inner water phase Doxil・Onivyde・Vyxeos Albumin and Medicine Particles No solvents Abraxane Block copolymer The nucleus and shell that can be assembled )xol-PM (Korea) Medicines in the polymer chain Sharing protein binding Oncaspar・SMANCS ※ Example of product name is Rosenblum et al (2018) [Reference Material 3], the composition of each product is FDA attachment [Reference Material 16-20], and the type classification is Duncan(2003) [Reference Material 12] and 　 Cabral et al (2018) The four parts are organized by this article and are not covered by all types. * Figures are imitations and do not indicate the ratio of the actual structure and particle size or the placement of the drug.
Fig. 1 Concept diagram (vector drawing).The example of the product name is Rosenblum et al (2018) [Reference Material 3], the composition of each product is FDA attached [Reference Material 16-20], and the classification of the type is based on Duncan(2003) [Reference Material 12] and Cabral et al (2018) [Reference Material 13].This article is divided into four sections.It does not indicate the ratio of actual structure or particle size.
TypeExample of approved products (FDA)Composition written in the attachmentUS Approval
PEG Qualified liposomeDOXIL
(Doxorubicin hydrochloride)		STEALTHLiposome. Cholesterol 3.19 mg/mL, hydrogen-added soybean phosphatidylicolin (HSPC) 9.98 mg/mL, MPEG-DSPE 3.19 mg/mL.More than of the drug is enclosed in liposomeNovember 17, 1995
PEG Qualified liposomeONIVYDE
English		DiameterApprox. 110 nmsingle layer liposome. DSPC 6.81 mg/mL, cholesterol 2.22 mg/mL, MPEG-2000-DSPE 0.12 mg/mL. Ilinotecan insideGelling or precipitation as a sucrose octasulphate saltContact UsOctober 22, 2015
Liposome(2 agents)VYXEOS
(Daunorbicin Shitarabin)		2 drugsMolar ratio 1:5Contact Us DSPC・DSPG・CholesterolMor ratio 7 :1Home 618 mg lipid gauge to 1 vial, copper gluconate 100 mg, sucrose 2,054 mgYear 2017
Albumin binding particlesABRAXANE
(Paclitaxel)		Average particle diameterApprox. 130 nmHome PaclitaxelAmorphousHome Paclitaxel 100 mg to 1 vial and human albuminApprox. 900 mg。No solvents2005 Year
Polymer-protein bindingONCASPAR
(Peace Paragase)		34.5nm consisting of four subunits of kDa,About 5 kDa mPEG 69-82ContactYear 1994

AllFacts(FDA attachment [Reference Material 16-20], Drugs@FDA [Reference Material 24/26], Year of each attachment "Initial U.S. Approval"); For VYX particle diameter and layer structure, An mo and Mitragotri are"100 nm double layer (bilamellar) liposome"Contact UsFacts[Reference Material 15].This article does not handle efficacy, effects and clinical results.

The general theory of Cabral about polymer micells"High-silica micelles combined with block copolymers and multi-molecular interactions with drugs, proteins, and nucleic acids"and Types of interaction between polymers and devicesHomeChemical and engineering of block copolymersWhen it comes to designFacts。 Use self-organization of surfactants for drug installationIt is the idea that This article explains.

3. Passive targeting and EPR effect – 1986 Report

The starting point of the idea of tumor nanocarriers is in Japanese studies. Yasuhiro Matsumura and Hiro Maeda, 1986Cancer Research This report was reported to the magazineFacts。

Article description (from the abstract of Matsumura and Maeda, 1986)

The starting point combined polymers into anticancer protein neocarcinostatinSMANCSHomeMore to the tumor tissue than the original neocarcinostatinIt was a preliminary discovery. Homeweight: 12,000 to 160,000I examined various proteins with radioactive labels,Many proteins gradually accumulate into the tumor tissue and the concentration ratio in the tumor and blood reaches 5 within 19–72 hoursFacts。

On the other hand, it is a representative of small proteinThe concentration of carcinostatin (2 weight 12,000) did not reach 1 or 5Facts。

Authors"The majority of blood is, the transmittance of polymers is increasing, and most of them are not recovered from blood and lymph."I guess according toFacts。

This isEnhanced Permeability and RetentionIt is a phenomenon called. Rosenblum“This phenomenon was written by Matsumura and Maeda in 1986 as the EPR effect.”Contact UsFacts。 "The larger the」, the more the tumor is accumulated."——This is the basis for passive targeting using nano carriers.

However, it doesn’t mean it’s too big.If it is too small, it will come out from the kidneys, and if it is too large, another problem will come out.

The size of the product: align the numbers that appear in the publication material to the scale Particle axes are particle diameter (nm). 10 times per scale 1 10 100 1,000 10,000 nm 5.5 nm If it is less than this retion to urine (quantity dot) 82〜241 Compared with animal experiments Liposome Diameter 100・110・130nm VYXEOS・ONIVYDE・ABRAXANE Neuralgia of the endothelial of the tumor Up to 2,000 nm * 5.5 nm is Choi et al (2007) [Reference 9], 82-241 nm is Charrois and Allen(2003) [Reference 10], 　 2,000 nm is based on the basics of Sindhwani et al (2020) [Reference Material 5]. * 110 nm and 130 nm are based on FDA attachments [Reference Material 17/18], 100 nm is based on An。mo and Mitragotri(2019) [Reference Material 15]. * 5.5 nm is the result of in nanoparticles (quantity dots) given to rodents, not the boundary for all particles.
Fig. 2 Concept diagram (vector drawing).Each number depends on Choi et al (2007) [Reference Material 9], Charrois and Allen (2003) [Reference Material 10], Sindhwani et al (2020) [Reference Material 5], FDA Attachment [Reference Material 17 · 18], An。mo and Mitragotri (2019) [Reference Material 15].This is a reference diagram of the number of different experiments arranged in one axis.It does not indicate the standard of "reach to the tumor if this range is"

Left End5.5 nmChoi et al."If the final hydrodynamic diameter is less than 5.5 nm, fast and efficient urine、retion is added."HOME Close"Twin-ionic or neutral organic coating prevents serum protein。orption. When orption occurs, the fluid dynamic diameter is more than 15 nm and the kidney retion was blocked.Facts。 The "actual size" of the particle changes just by making protein on the surface——This point is taken again in Chapter 6.

About the center range, Charrois and Allen diameter82、101、154、241 nmCompare the liposome with the mouse, Smaller 3 species showed similar umulation, both were significantly more than 241 nmReportFacts。

4. Discussing EPR Effects: What Does Not Work for Humans?

The EPR effect was the premise of nanopharmaceu、 design for more than 30 years. However, since the latter half of the 2010s, there is a paper questioning the premise. Here we do not raise the military distribution on the left side of the paper.

PublicationsClaim (Summary/B Description)Position (organization by this article)
Wilhelm et
（2016）		When the past 10 years of literature is aggregated,"Reaching a solid tumor of the nanoparticles received is only 0.7% at the center value"Home This lowEffects of manufacturing, cost, toxicity, imaging and treatmentnegativetify the small amount of delivery
Danhier
（2016）		“EPR effects work in rodents, but not work in humans”HOMEDon’t claim to improve EPR effectivenessCommentEPR effect negative
Rosenblum
（2018）		0.7% is small, but"Really, the delivery efficiency of conventional drugs (docetaxel, paclitaxel, doxorubicin, etc.) in the mainstream in clinical practice is significantly higher."Home Example: Paclitaxel enclosed nano carrier0.6%IDFree Paclitaxel0.2%IDPre ical ResearchThe absolute value is low but has a relative advantage
Sindhwani et
（2020）		The gap between the endothelial cells of the tumor (up to 2,000 nm) does not transport nanoparticles to tumors."Up to 97% nanoparticles enter the tumor in a dynamic process that passes through the endothelial cells"Asking the mechanism of "leaking out of the gap" itself

AllFacts(Wilhelm et al [Reference Material 2], Danhier [Reference Material 4], Rosenblum et al [Reference Material 3], Sindhwani et al [Reference Material 5]). The column of "position" is organized by this article, not by each author.

There are examples of human measurement. Rosenblum19 patients with HER2-positive metastatic milk cancerRadioactive copper (in)64This page introduces the research identified by PET/CT. 24 to 48 hoursso that the patient can be grouped in the aggregate amountFactsHome This paper also accumulates in tumors.UnevenAn animal experiment that indicates thatFacts。

Substitute the discussion with the words of the material (in this article)

The confrontation here is"How much tumor producibility and which tumors do?"Comment Rosenblum’s human data indicates the collectionBulking per patientSo, ItPre- imaging by ImageThe direction is also discussed. Materials making of materials,"Paints that are not attached by base material"It is a composition that is close to the problem of how to handle.

5. Sulation: 0.7%

This paper's description of

Let's convert a number of published values.This paper's description of。

  • Premise:The median 0.7% of the dosage is delivered to solid tumors (Wilhelm, etc.)Facts
  • Tumors:100 − 0.7 ＝ 99.3%
  • Tumor ratio:99.3 ÷ 0.7 ＝ Approx. 142 times
  • Relative improvements (e.g. Rosenblum):0.6% ÷ 0.2% ＝ 3 times

Premises and Limits:0.7%The median value of animal experiments (mainly mouse)not human life. In addition, "the amount to go outside the tumor" includes all the minutes captured by the liver and spleen, the minutes leaked from the kidneys, and the minutes left in the blood. I don’t know where to go. The ratio of three times is also one pre。ical study.

Delivered nanoparticles to solid tumors (including calculation of this article) 0.7% The amount delivered to solid tumors (center) Ag ation of animal experiments in the past 10 years Wilhelm et al public Approx. 142 times The amount to go outside of the tumor (tumor ratio) 99.3 ÷ 0.7 ＝ 141.9 This paper's description of 3 times The amount delivered compared to free medicine 0.6% ÷ 0.2% This paper's description of 100 destinations when sent out ← 0.7 pieces of red slim band. 99.3 of the rest except for tumors such as liver, spleen, kidney, and blood * 0.7% is a pre- ical research by Wilhelm et al (2016) [Reference Material 2], 0.6% and 0.2% is a research by Rosenblum et al (2018) [Reference Material 3]. * About 142 times and 3 times are calculated by this article, not publicly available. It is not a human life because it is an animal experiment. * The length of the band is 0.7% proportional.
Figure 3 Drawing including calculation of this paper (vector drawing).0.7% depends on Wilhelm et al (2016) [Reference Material 2], 0.6% and 0.2% depend on Rosenblum et al (2018) [Reference Material 3].142x and 3x are calculated by this article.Both of them are animal experiments and do not show human delivery or the effect.

6. Material Technician Perspective 1: Deciding the remaining 99% is “surface”

The reading of the material ian: the moment you enter the blood, the surface of the particle becomes "another material"

Rosenblum et al al al al al al al al al al al al al al al"Most of the nano carriers are eliminated by the mononuclear cell system (MPS). Some are physically excreted into the liver's bile ducts, and some are taken into the liver and upper liver cells."FactsHome and as a factor that affects the efficiency of targeting"Cover formed by serum protein and opsonine (also called protein content)"HomeFacts。

The cells in the body are “seeing” is not the surface of the designed particle, but the layer of protein ad ed thereComment This article explains. The result of Choi in Chapter 3:Prevent protein uptake with bispecific or neutral coatings, where the fluid dynamic diameter is more than 15 nm when the protein adsorbs to the surface.FactsDutchSurface chemistryindicates that there is a road.

This is a tool that is familiar with material engineers.Surface modification by PEG (poly) coatingsComment FDA doxorubicin liposome product guidance“Methoxy、、l (MPEG) coated on the surface protects liposom from mononucleic cell removal and extends blood circulation time.”HOME "The thickness of the PEG layer is limited to thermodynamics and can be quoted as a few nanometers."Contact UsFacts。

Numerous nanometers of polymeric brushes depend on the destination in the bodyDutch This isDistributed Stabilizer, Anti-fouling CoatingEngineers who have been should have a familiar world (in this article). OtherA place of evaluation is in the body with plasma containing thousands of proteins, not "stain"Comment

7. Active targeting and liganding — not the amount to collect, the way to enter

While passive targeting relies on the size,Active targetingis on the surface of the particlesRegulations for active targeted nanocarriers and relatively complex manufacturing scale up(parts that combine to specific。s). Rosenblum"In active cell targeting, the affinity ligand is attached to the surface of the nano-carrier, aiming for specific umulation, increased gnation at the target site, and taking in target cells."HOME As an opponent of ligandHER2, folate receptor, CD44OtherFacts。

“Nano carriers that are actively targeted must first reach the target. therefore efficient passive targeting is the prerequisiteNotedFacts。 ligand does not pull the particles to the tumorIt is. The following two reports:

ResearchWhat to compareTumor umulation to tumorsBinding and importing into cells
Kirpotin
（2006）		Long-circulating liposome combined with anti-HER2 antibody fragments (Fab′ or scFv) at the tip of PEG chain, and non-binding liposomes (HER2 overexpressed human milk cancer heterogeneous transplantation mouse)Both are equally high (7 to 8% ID/g)Home Binding of antibody fragments did not change the body distribution and long circulationTargetedIn cancer cellsNoneInterstitial and MacrophageHome Intake in cancer cellsUp to 6 times
Moreira et
（2001）		Stealth liposome combined with peptide (antagonist G) on the surface, and liposome (human small cell lung cancer heterogeneous transplantation mouse)dependent on the size of the liposome, but did not depend on whether the ligand isHome Maximum 2-4 % ID/gBinding cells from tumors30 to 44 times

AllFacts(Kirpotin et al [Reference Material 6], Moreira et al [Reference Material 7]) AllMouse resultsComment %ID/g is a unit representing how many % of dosage per g of tissue.

The ligand changes the way to enter, not the amount to collect ulation of the mouse experiment of Kirpotin et al (2006) No ligand (passive targeting) Antibody fragmentation Outside of cancer cells (tea) Most people stay Cancer cells Contact Us Tumor umulation to tumors 7〜8%ID/g Macrophage Tumor umulation to tumors 7〜8%ID/g Cancer cells Max. 6 times The tumor is carried with "size and surface", and the ligand is effective with "first" * 7 to 8% ID/g, distribution of intracellular, interstitial and macrophage, up to 6 times depends on the principal of Kirpotin et al (2006) [Reference Material 6]. The result of the mouse. * The number and placement of particles are imitation, and it does not indicate the actual distribution or ratio. Below is a summary of this article.
Figure 4 Concept diagram (vector drawing).The magnification of umulation, distribution, and import depends on the principal of Kirpotin et al (2006) [Reference Material 6].The number and placement of particles are imitation, and the summary of the lower part is based on this article.It is a result of a mouse, and it is not possible to occur the same thing in humans.

and clinical results. As of 2018,“The passive targeted nano-carrier is approved by 15 clinical use, but the active targeted type does not exceed the stage of clinical trials.”FactsHome For the nanoparticles BIND-014 of docetaxel targeting PSMA,Two phase tests failed to achieve major evaluation itemsContact UsFactsHome In addition to barriers such as penetration to the tumor, unevenness of the tumor, hypoxia, and escaping from the endsome, the paper is the background of the paper. "Regulations for active targeted nanocarriers and relatively complex manufacturing scale-up"HomeFacts。

We have also reported the ingenuity of the manufacturer. Moreira et al , peptide ligandMicelle binding at the end of PEG lipidsHowever, itRadiated with radioactive ruthenium through D chelateTest lipid per 1 μMax. 0.3 μgThe liposome with the ligand has been reported to indicate cell injuries that are similar to conventional binding methodsFactsHome At the beginning"In order to apply clinical trials, it is necessary to make ligand targeted liposoms large scale."Facts。 Is it possible to separate the process of making particles and the process of putting ligands?However, you can see that scale-up is the point (in this article).

8. In small s, active targeting is product

Not all targets using ligands fail. Gan ligands to the drug itself rather than ligands to particlesThere are approved products in the form.

ProductRegulations for active targeted nanocarriers and relatively complex manufacturing scale upCarryingFirst approval in the United States
GIVLAARI
（givosiran）		N-acetyl galactosamine (GalNAc)3 residueincluding ligands.To deliver to liver cellsShared binding to siRNAsiRNAYear 2019
PLUVICTO
（lutetium Lu 177 vipivotide tetraxetan）		Regund binding to PSMARadiolabeled with radioactive uranium through a chelateRadioactivity 177Lu (molecular weight 1,216)2022 year
Antibody Drug Complex (ADC)AntibodyDance is also a human biological equivalent test.This series "Antibody Drugs and ADCs" are handled in detail.

GIVLAARI・PLUVICTOFacts(FDA attachment [Reference Material 22 & 23] Initial U.S. ApprovalThis article does not handle efficacy, effects and clinical results.Nucleic acid drugs using GalNAc are handled in detail in this series.

Why do small)s work well?

Chapter 7The size and surface of the particle was determined to reach the tumorThen, the ligand was effective after reaching. On the other hand,If the transport is small and its itself spreads to the organization, the binding of the ligand is directly effective in the choice of destinationI think. Gal weight of GalNAc-siRNA is about 16,000FactsThe size of 100 nm liposome is different. However,The primary information that directly compares why it was successful was not confirmed within the scope of the survey.This page is a read of this article, which expresses the facts published.

On the dark side, the concept image that the slight balls of the white smooth size scattered around the eye
Figure 5 Concept diagram (AI generation image).It expresses the idea of "drug into a microsphere of polymers and release it slowly."It does not indicate actual product, particle size, surface condition, and microscope image.

9. Emission control - E tion is determined

Another pillar of DDSEmission ControlHome Read the attachments and papers of approved products,What state of medicine is ped?However, you can see that the product is completely different.

(1) Make "cr」al" and "salt" in liposome

BarenholzThree unrelated principlesIt is organized as it is based onFacts。

  • PEG qualified nano liposomeElongation of blood circulation time and avoidance of sludge
  • Ammmonium sulfate concentration gradient inside and outside of the membrane"Remote loading" of high stable doxorubicin with driving force. This enables the release of tumors.
  • Phosphatidylcholine and cholesterol with high phase transition temperature (53°C)by "liquid order phase" lipid double membrane

FDA Product dance."Doxorubicin is mainly used in the form of crystals of doxorubicin sulfate inside liposomes."Contact UsFactsHome ONIVYDEGel or precipitated condition as a sucrose octasulfate salt.enclosed inFacts。 Make medicines close to solids in a bag and reduce leaks——The control of crystallization and sedimentation is released as it is (in this article).

(2) Embed into microspheres of biodegradable polymers

LUPRON DEPOT 3.75 mgFreeze Dry Microsphere (Microsphere) PowderHome ruproleline 3.75 mg, purified gelatin 0.65 mg,DL-Lactic acid and coolelic acid copolymer (PLGA) 33.1 mg.D-mannitol 6.6 mgFacts。 1 injection per monthIt is a formulation that continues to effectFactsHome LUPRON DEPOT (NDA 0、2)January 26, 1989Facts。

Fredenberg et al.“PLGA is a biodegradable polymer that is most frequently used for the release control of enclosed drugs.”HOME "The drug release from DDS using PLGA is complex", "It is difficult to predict the generalization and release of results due to its complexity"Facts。

(3) Binding to polymers to change the size itself

ONCASPARAbout 5 kDa mPEG 69-82Joining, EnzymeFactsHome Chapter 3: "It is hard to get out of the blood as large molecules."By combining polymers and increasing toIt is the shape used ( This article explains. Matsumura and Maeda SMANCS also combines polymers into proteinCommentFacts。

What type of medicine is ped in? - Three types of release control 1 Solidification in bag 2 Filling into polymer dissolving 3 Binding polymers Internal and external ion concentration difference In medicine. Crystal, Salt, Gel DOXIL・ONIVYDE PLGA Disperse drugs Emission mechanism is complex LUPRON DEPOT Multiple chains such as PEG Increase s Easy to stay in the blood ONCASPAR・SMANCS *1: Barenholz (2012) [Reference Material 11], FDA Product dance [Reference Material 28], ONIVYDE Attachment [Reference Material 17], and LUPRON DEPOT Attachment [Reference Material 21]. 　 Fredenberg et al (2011) [Reference Material 14], 3 is based on ONCASPAR attachment [Reference Material 20], Matsumura and Maeda(1986) [Reference Material 1]. * This article is divided into three articles. The figure is imitation and does not indicate the number of actual crystals, particle diameters and chains.
Figure 6 Concept diagram (vector drawing).1 is Barenholz (2012) [Reference Material 11], FDA Product dance [Reference Material 28], ONIVYDE Attachment [Reference Material 17], 2 is LUPRON DEPOT Attachment [Reference Material 21], Fredenberg et al (2011) [Reference Material 14], 3 is based on ONCASPAR Attachment [Reference Material 20], Matsumura and Maeda [Reference Material 1].The three types are organized by this article.

10. The calculation of this paper: What is the weight of the drug?

First, the number to be attached
  • DOXIL (per mL):Doxorubicin hydrochloride 2 mg/cholesterol 3.19 mg/HSPC 9.58 mg/MPEG-DSPE 3.19 mg/sucrose 94 mg.Facts
  • ONIVYDE (per mL):irinotecan (free base) 4.3 mg/DSPC 6.81 mg/cholesterol 2.22 mg/MPEG-2000-DSPE 0.12 mgFacts
  • VYX)(1 vial):Dounolbicin 44 mg cytarabine 100 mg/DSPC 454 mg/DSPG 132 mg/cholesterol 32 mg/suc 2,054 mgFacts
  • ABRAXANE(1 vial):Paclitaxel 100 mg/human albumin about 900 mgFacts
  • LUPRON DEPOT 3.75 mg：Luporrin Acetate 3.75 mg/PLGA 33.1 mgFacts
  • ONCASPAR：34.5 kDa subunit 469s, about 5 kDa mPEG 69-82Facts
This paper's description of

From the above numbersWhat is the mass of the material on the transport side of the drugConvertThis paper's description of。

  • DOXIL：Total fat 3.19+9.58+3.19 = 15.96 mg. 15.96 ÷ 2 = 8.0 timesHome PEG lipids (MPEG-DSPE) are 3.19 ÷ 15.96 = About 20%
  • ONIVYDE：Fat Total 6.81+2.22+0.12 = 9.15 mg. 9.15 ÷ 4.3 = About 2.1 timesHome PEG fat is 0.12 ÷ 9.15 = About 1.3%
  • VYXEOS：Fat Total 454+132+32=618 mg, total of the drug 44+100=144 mg. 618 ÷ 144 = 4.3 times
  • ABRAXANE：900 ÷ 100 ＝ Approx. 9 times(Albumin / Paclitaxel)
  • LUPRON DEPOT 3.75 mg：33.1 ÷ 3.75 ＝ 8.8 times(PLGA/Drug)
  • ONCASPAR：Enzyme 34.5 × 4 = 138 kDa, PEG 5 × 69~82 = 345~410 kDa. PEG 345 ÷ 483 = 71% - 410 ÷ 548 = , that isAbout 70% of mass is PEG

Premises and Limits:DOXIL is a hydrochloride and ONIVYDE is compared with the mass of free base, and the shape of the salt is not affected. ABRAXANE’s "approx. 900 mg" is an approximate number of attachments, including sodium caprylate and sodium acetyl tryptophan. ONCASPAR’s weight is a simple calculation from the subunit molecular weight of the attachment and the weight of mPEG. Both are intended to see the composition of the formulation from the viewpoint of the material, and do not compare the effect or safety.

What is the weight of the drug? The length of the rod is proportional to the magnification (1x = 50). The number is calculated from the description of the attached document. ABRAXANE LUPRON DEPOT DOXIL VYXEOS ONIVYDE Approx. 9 times 8.8 times 8.0 times 4.3 times About 2.1 times AL. PLGA Fat (PEG fat about 20%) Oil Oil Reference: ONCASPAR is about 71 to 71 of the mass of the connecter PEG (about 2.5 to 3.0 times of the ) * The mass of each component is the FDA attachment [Reference Material 16-21]. The magnification and centrifuge are calculated by this article, not the published value. * DOXIL is comparable to the mass of free base. Additives such as suc。 are not included. * The composition from the viewpoint of the material is not comparable to the effect and safety of the product.
Figure 7 Drawings including calculation of this paper (vector drawing).The mass of each component depends on the FDA attachment [Reference Material 16-21].The magnification and the centrifuge are calculated by this article, not the published value.Please note that it does not contain additives such as salt or suc .

11. Material Technicians’ Perspective 2: Read the FDA’s Guidelines for the 17-year-old reason for later products

The reading of the material ian: Even if the same component is put in the same amount, it is not suitable for the same thing

Drugs@FDA approved DOXIL (NDA 050718)November 17, 1995Approval of Sun Pharma, ANDA 203263)February 4, 2013HomeFactsHome The differenceAbout 17 years and 2 monthsHomeThis paper's description ofHome Barenholz is a general theory of 2012,"Doxil has not been issued after FDA approved even after two years from the expiration of related patents."I wroteFacts。

How long does it take? Doxorubicin liposome published by the FDA.Product dance by Product (Draft of Revised May 2022).Read MoreThe conditions required for subsequent products are the requirements specification of materials and processes.I knowFacts。

  • Composition:Additives and predecessorsQualitatively Same (Q1)ConcentrationWithin ±5% (Q2)
  • Method:Active e by ammonium sulfate gradientto manufacture. The main process is the formation of liposomes containing ammonium sulfate → reduction of particle diameter → formation of ammonium sulfate gradient → active envel of the drug
  • Fat Raw Material:“The lipid additive is definitively important in liposome preparations.”Home ProductsSegment of the same path (natural or )not only to meet standards, but also to use lipidstype distributionto compare
  • Compared characteristics:Composition of liposome,Enclosed medicine conditions (crystals of doxorubicin sulfate).Internal environment (volume, pH, sulfate, ammonium ion concentration),Forms and Rameras、Lipid double membrane phase transitionParticle size distribution,Surface PEG Layer ThicknessSurface potential,Leakage in multiple conditions
  • Particle Diameter Distribution:D10・D50・D90D50 and SPAN〔(D90-D10)/D50〕Determines the equivalent. Predecessor and postpartum products30 vials or more

This is not the same component table, but the same internal structure and interface. Crystal state, membrane phase behavior, surface polymer layer thickness, particle size distribution - bothMateriality moving in process conditionsHome dance"Identify important process parameters and important material properties by evaluating the sensitivity of liposome properties"RecommendedFacts。

For the side measuring lipids,It is possible to ask that the distribution of molecular species is the same as the predecessor.That is important. Natural origin orRaw materialHowever, it is a condition of the equivalent of the product. This article explains. In this series "Biosimilar", we will explain how the same problem is treated with biological preparations.

What is taken to say "the same" in the subsequent liposome formulation (conception diagram) FDA Doxorubicin Liposome Product dance (Draft Revised May 2022). Entrance requirements Additives are qualitatively the same (Q1). Within ±5% concentration (Q2) Ammonium Su ate Gradient Dynamically enclosed manufacturing methods Fat is the same path segment. Comparison of distribution of species Home Composition, e rate, drug and lipid ratio Crystals of doxorubicin sulfate. Internal volume, pH, ion concentration Membrane Forms and Rameras Lipid double membrane phase transition Leakage of drugs in multiple conditions Surface PEG layer thickness (approx. nm) Surface potential and charge Size D10・D50・D90 D50 and SPAN 30 vials or more Approval of first item November 17, 1995 → Approval of first postpartum February 4, 2013 (approx. 17 years and 2 months) * Comparative items are based on FDA Product [Reference Material 28] and Drugs@FDA [Reference Material 24 & 25]. This article is calculated for 17 years and 2 months. * This article is divided into four boxes. Protein-protein interactions are also a human biological equivalent test.
Figure 8 Concept diagram (vector drawing).Comparative items are based on FDA Product [Reference Material 28] and Drugs@FDA [Reference Material 24 & 25].It is the period calculated by this article about 17 years and 2 months.Dance does not explain why it took time to develop later products.

12. Issues and Undetermined

(1) EPR effect is not determined

As seen in Chapter 4The significance of the EPR effect is greatly divided by the paperHome Sindhwani et al understand the active pathway through endothelial cells"Open a strategy to increase tumor accumulation"Facts、 Products that use the pathway to increase clinical delivery were not confirmed at the time of the investigation of this article (September 2026)Undetermined / Future。

(2) Clinical value of ligands attached to particles

Rosenblum et al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al alFacts、 As of September 2026, the same product has been approved by the FDA.Undetermined / Future。

(3) Patient ing

Rosenblum et al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al , al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al al alFacts。 Primary information that indicates that this has been established as a standard procedure of clinical was not confirmed in the scope of this articleUndetermined / Future。

This article
  • DDS is the technology of “how to carry”.Liposome, albumin particles, polymer micelles, polymer joiners, etc.Facts
  • EPR was reported in Japan in 1986.Proteins of polymers reached 5 in 19–72 hours in the tumor and in the bloodFacts
  • The amount to be delivered is 0.7% (ag ation of animal experiments).The amount other than the tumor is about 142 times the tumorThis paper's description of
  • Even if the ligand occurs, the amount of tumor accumulation does not change, the intake into the cell changesThere is a mouse report called ——Facts
  • In approved products, the material of the transport side is about 2-4% of the drug's mass.This paper's description of
  • In addition to the composition table, the equivalent of "in structure and interface" is required for the latter product.DOXIL takes about 17 years and 2 months to the first postpartumThis paper's description of

13. Glossary

DDS
Drug delivery system. Technology to control the destination and speed of release of the drug.
Nano Career
Nanometer-sized particles and polymers that can be wrapped or combined with drugs.
Liposome
Small bag made of lipid double film. Put the medicine in the inner water phase and membrane.
Micro-high
A particle with a nucleus and shell that blocks copolymers can self-structure.
Polymer Bonding
Sharing medicines and proteins into polymer chains. PEG protein, etc.
Passive targeting
Make it easier to gather in specific tissues by using the size of the particles and the properties of the surface.
Active targeting
Binding and importing ligand cells with specific receptors.
EPR Effect
A phenomenon where polymers and particles are easily leaked to the tumor. Matsumura and Maeda reported in 1986.
Regulations for active targeted nanocarriers and relatively complex manufacturing scale up
Components that selectively bind to specific s (such as receptors). Antibody, peptide, sugar, etc.
Protein
A layer of protein ad ing to the surface of the particles in the blood. Change the properties of particles.
Mononucleic cell system (MPS)
The mechanism of cells that take and remove foreign objects such as liver and spleen.
PEG
poly l. Reduce coagulation and removal, extend blood retention.
%ID/g
Unit showing how many % of dosage per g of tissue.
Remote loading
Using the ion concentration difference inside and outside the membrane, the sealing method to bring the medicine into the finished liposome.
PLGA
Copolymer of l acid and lic acid. It is a polymer that is dissolved in the body and is used for slow release agent.
Q1／Q2
Subsequent product additives are qualitatively the same as predecessors (Q1) and concentration is within ±5% (Q2).
SPAN
Indicator of spread of particle size distribution. (D90-D10)/D50

14. Reference Materials

  1. Matsumura, Y., Maeda, H.「A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs」Cancer Research 46(12 Pt 1), 6387–6392 (1986). PMID 2946403 — pubmed.ncbi.nlm.nih.gov
  2. Wilhelm「Analysis of nanoparticle delivery to tumours」Nature Reviews Materials 1, 16014 (2016). doi:10.1038/natrevmats.2016.14 — nature.com
  3. Rosenblum, D., Joshi, N., Tao, W., Karp, J.M., Peer, D.「Progress and challenges towards targeted delivery of cancer therapeutics」Nature Communications 9, 1410 (2018). doi:10.1038/s41467-018-03705-y — nature.com
  4. Danhier, F.「To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?」Journal of Controlled Release 244(Pt A), 108–121 (2016). doi:10.1016/j.jconrel.2016.11.015 — pubmed.ncbi.nlm.nih.gov
  5. Sindhwani「The entry of nanoparticles into solid tumours」Nature Materials 19(5), 566–575 (2020). doi:10.1038/s41563-019-0566-2 — pubmed.ncbi.nlm.nih.gov
  6. Kirpotin, D.B.「Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models」Cancer Research 66(13), 6732–6740 (2006). doi:10.1158/0008-5472.CAN-05-4199 — pubmed.ncbi.nlm.nih.gov
  7. Moreira, J.N., Gaspar, R., Allen, T.M.「Targeting Stealth liposomes in a murine model of human small cell lung cancer」Biochimica et Biophysica Acta 1515(2), 167–176 (2001). doi:10.1016/s0005-2736(01)00411-4 — pubmed.ncbi.nlm.nih.gov
  8. Moreira, J.N., Ishida, T., Gaspar, R., Allen, T.M.「Use of the post-insertion technique to insert peptide ligands into pre-formed stealth liposomes with retention of binding activity and cytotoxicity」Pharmaceutical Research 19(3), 265–269 (2002). doi:10.1023/a:1014434732752 — pubmed.ncbi.nlm.nih.gov
  9. Choi, H.S.「Renal clearance of quantum dots」Nature Biotechnology 25(10), 1165–1170 (2007). doi:10.1038/nbt1340 — pubmed.ncbi.nlm.nih.gov
  10. Charrois, G.J., Allen, T.M.「Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity」Biochimica et Biophysica Acta 1609(1), 102–108 (2003). doi:10.1016/s0005-2736(02)00661-2 — pubmed.ncbi.nlm.nih.gov
  11. Barenholz, Y.「Doxil® — The first FDA-approved nano-drug: Lessons learned」Journal of Controlled Release 160(2), 117–134 (2012). doi:10.1016/j.jconrel.2012.03.020 — pubmed.ncbi.nlm.nih.gov
  12. Duncan, R.「The dawning era of polymer therapeutics」Nature Reviews Drug Discovery 2(5), 347–360 (2003). doi:10.1038/nrd1088 — pubmed.ncbi.nlm.nih.gov
  13. Cabral, H., Miyata, K., Osada, K., Kataoka, K.「Block Copolymer Micelles in Nanomedicine Applications」Chemical Reviews 118(14), 6844–6892 (2018). doi:10.1021/acs.chemrev.8b00199 — pubmed.ncbi.nlm.nih.gov
  14. Fredenberg, S., Wahlgren, M., Reslow, M., Axelsson, A.「The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems — a review」International Journal of Pharmaceutics 415(1-2), 34–52 (2011). doi:10.1016/j.ijpharm.2011.05.049 — pubmed.ncbi.nlm.nih.gov
  15. Anselmo, A.C., Mitragotri, S.「Nanoparticles in the clinic: An update」Bioengineering & Translational Medicine 4(3), e10143 (2019). doi:10.1002/btm2.10143 — pmc.ncbi.nlm.nih.gov
  16. FDA／NLM DailyMedDOXIL (doxor cin hydrochloride liposome injection) dailymed.nlm.nih.gov
  17. FDA／NLM DailyMed"ONIVYDE (irinotecan liposome injection)" — dailymed.nlm.nih.gov
  18. FDA／NLM DailyMedABRAXANE (paclitaxel protein-bound particles) dailymed.nlm.nih.gov
  19. FDA／NLM DailyMed"VYX (daunor cin and cytarabine liposome)" — dailymed.nlm.nih.gov
  20. FDA／NLM DailyMedONCASPAR (pegaspargase) dailymed.nlm.nih.gov
  21. FDA／NLM DailyMedLUPRON DEPOT 3.75 mg (leupro for depot suspension) dailymed.nlm.nih.gov
  22. FDA／NLM DailyMed"GIVLAARI (givosiran) Attachment" — dailymed.nlm.nih.gov
  23. FDA／NLM DailyMedPLUVICTO (lutetium Lu 177 vipivotide 177xetan) dailymed.nlm.nih.gov
  24. FDA Drugs@FDANDA 050718 DOXIL (LIPOS)」L) Approval History — accessdata.fda.gov
  25. FDA Drugs@FDA"ANDA 203263 Doxor cin Hydrochloride (liposomal), Sun Pharma" Approval History — accessdata.fda.gov
  26. FDA Drugs@FDANDA 20」3 ONIVYDE Approval History — accessdata.fda.gov
  27. FDA Drugs@FDANDA 0」2 LUPRON DEPOT Approval History — accessdata.fda.gov
  28. FDA"Draftance on Doxorubicin Hydrochloride (Injectable, liposomal)" Product, May 2022 (PDF) — accessdata.fda.gov

15. Response Table of Claim and Sources (Audit)

ContentHome
Preliminary discovery that SMANCS (combined polymers in neocarcinostatin) gathers more in the tumor tissue than the original neocarcinostatin. Using proteins of 2 weights of 12,000 to 16 million, many gradually accumulate in the tumor tissue and reached 5 within 19–72 hours of concentration in the tumor/blood. Carcinostatin (2 weight: 12,000) did not reach 1 or 5. I guessed that there is a large number of blood, hypertransmittance to polymers, low recovery from blood, and lymphatic. YearMatsumura and Maeda(1986)Source 1 https://pubmed.ncbi.nlm.nih.gov/2946403/Facts
In the ag ation of the past 10 years of literature, the central value of 0.7% of the nanoparticles delivered to solid tumors is negatively affecting the production, cost, toxicity, imaging and treatment effectsWilhelm et al (2016)Source 2 https://www.nature.com/articles/natrevmats201614Facts
Examples of clinically used passive targeted nanocarriers (US Doxil, Abraxane, Marqibo, DaunoXome, Onivyde, Europe Myocet, Mepact, South Korea olxol-PM, Japan SMANCS). The EPR effect was first described by Matsumura and Maeda in 1986. There are 15 approved passive targeting types and 0.7% of active targeting types are still undergoing clinical trials (as of 2018). Examples of preclinical studies of 0.6% ID and 0.2% ID that 0.7% is valued by meta-analysis of preclinical data, and that 0.7% is relative to the delivery efficiency of conventional preparations. Removal by MPS, capturing the liver to the bile ducts, and taking it with liver cells and upper liver cells. Improve targeting efficiency. The definition of active targeting and the opponent of ligand (HER2, folic acid receptor, CD44) must be the prerequisite for efficient passive targeting. Barriers (tumor penetration, unevenness, hypoxia, endosom escape) and the complexity of regulatory rules and manufacturing scale-ups. BIND-014 failed to achieve major evaluation items in two phase tests. 19 patients with HER2-positive metastatic breast cancer were identified with 64Cu-labeled liposomes using PET/CT and peaked at 24 to 48 hours. Animal experiments that show uneven accumulation. How to choose a patient with an imaged EPR evaluationRosenblum et al (2018)Source 3 https://www.nature.com/articles/s41467-018-03705-yFacts
The EPR effect is determined that it is not working in rodents but not working in humans. It is said that it is necessary to stop insisting the improvement of effectiveness by the EPR effect.Danhier (2016)Source 4 https://pubmed.ncbi.nlm.nih.gov/27871992/Facts
The gap between the endothelial cells of the tumor has been up to 2,000 nm, that the gap does not transport the nanoparticles to the tumor, that up to 97% of nanoparticles enter the tumor in the active process through the endothelial cells, and the understanding of the pathway is to open a strategy that increases the cumulativeSindhwani et al (2020) abstractSource 5 https://pubmed.ncbi.nlm.nih.gov/31932672/Facts
The long-circulating liposome that combined anti-HER2 antibody fragments (Fab′ or scFv) into PEG chains did not change the body distribution and long-circulatory properties, and the tumor was accumulated between 7 and 8% ID/g with or without targeting, and the targeted ones were mainly present in interstitial and macrophages, up to 6 times the intracancer cells.Kirpotin et al (2006)Source 6 https://pubmed.ncbi.nlm.nih.gov/16818648/Facts
Stealth liposomes combined with antagonist G joined the tumor-derived cells 30 to 44 times higher, and the tumor's accumulation depended on the size of the liposomes and not on whether the ligand existed, up to 2 to 4% ID/g.Moreira et al (2001) abstractSource 7 https://pubmed.ncbi.nlm.nih.gov/11718672/Facts
A post-injection method that transfers peptide ligands to existing liposomes from micelles combined at the end of the PEG lipid, and liposomes containing up to 0.3 μg of ligands per 1 μg of lipids have been shown to have cell injuries similar to conventional binding methods. Clinical trials require a simplified way to make ligand-targeted liposomes for large-scale production.Moreira et al (2002) abstractSource 8 https://pubmed.ncbi.nlm.nih.gov/11934232/Facts
A rapid and efficient urinary retention of less than 5.5 nm in the final hydrodynamic diameter, a bisexual or neutral organic coating prevents serum protein orption, fluid orption that the fluid dynamic diameter was blocked by 15 nm ultra-high-definition urinary retention, and the dot was given to the tooth.Choi et al (2007)Source 9 https://pubmed.ncbi.nlm.nih.gov/17891134/Facts
Compared to the liposome of 82, 101, 154, 241 nm diameter with the mouse, the small three species showed the same amount of umulation and significantly more significant than the maximumCharrois and Allen(2003)Source10 https://pubmed.ncbi.nlm.nih.gov/12507764/Facts
DOXIL is the first FDA-approved nanopharmaceu。 approved in 1995. It is based on the three principles: PEG-modified nano liposome circulating time extension, remote loading by ammonium sulfate gradient, high phase transition temperature (53°C), and liquid order phase membrane by cholesterol. 2 years after the patent expired, there was no subsequent product (as of 2012)Barenholz (2012)Source11 https://pubmed.ncbi.nlm.nih.gov/22484195/Facts
Polymeric drugs, a nano-size (5-100 nm) polymeric drug, contains polymers - drug bindings, polymers - protein bindings, polymer micelles that share drugs, and polyplexes for DNA delivery.Duncan(2003)Source12 https://pubmed.ncbi.nlm.nih.gov/12750738/Facts
The core of the design is the chemical and engineering of block copolymers and block copolymers.Cabral et al (2018)Reference13 https://pubmed.ncbi.nlm.nih.gov/29957926/Facts
PLGA is the most frequently used biodegradable polymer for emission control of enclosed drugs, the complexity of emission and difficulty in generalization and predictionFredenberg et al (2011)Reference14 https://pubmed.ncbi.nlm.nih.gov/21640806/Facts
VYX is 100 nm double layer (bilamellar) liposomeAn mo And Mitragotri(2019)Source15 https://pmc.ncbi.nlm.nih.gov/articles/PMC6764803/Facts
DOXIL encapsulated doxorubicin hydrochloride into ST TH liposomes, 2 mg doxorubicin hydrochloride per mL, 3.39 mg cholesterol, 9.58 mg PC, MPEG-DSPE 3.19 mg, containing 94 mg of sucrose, if more than 1995 of the drug is enclosed, Initial U.S. Approval is 1995.DOXILSource16 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1c153e9e-4cf2-4ac7-9cf9-16f9b48d7dceFacts
ONIVYDE is a single-layer liposome with a diameter of about 110 nm, including irinotecan gelled or precipitated as a sucrose salt, containing 4.3 mg per mL, DSPC 6.81 mg, cholesterol 2.22 mg, MPEG-2000-DSPE 0.12 mg.ONIVYDESource17 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c8b58efa-1820-48a4-b70d-62918fc4abfcFacts
ABRAXANE is an average particle diameter of about 130 nm, which is a pacrytaxel amorphous and contains no solvents that contain 100 mg of paclitaxel and 900 mg of human albumin in vials. Initial U.S. Approval is 2005.ABRAXANESource18 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d10449-2936-4cd3-b7db-a7683db721e4Facts
VYX membrane encloses doxorubicin and cytarabine in a ratio of 1:5 and the membrane is 7:1 of DSPC, DSPG, cholesterol, 44 mg of doxorubicin, 100 mg of cytarabine, 454 mg of DSPC, 132 mg of DSPG, 32 mg of cholesterol, 100 mg of gluconate, including 2,054 mg of sucrose, Initial U.S. Approval is 2017.VYXSource 19 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ea701ce-e7d3-4349-a9c2-642a501d45c8Facts
Initial U.S. Approval is 1994.ONCASPARSource20 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac7b6a6f-6ddb-48c6-8088-d8a8e3fea6ceFacts
LUPRON DEPOT 3.75 mg is a freeze-dried microsphere powder that contains leuproline 3.75 mg, purified gelatin 0.65 mg, DL-lactolic acid and colesevelam copolymer 33.1 mg, D-mannitol 6.6 mg per month.LUPRON DEPOT 3.75 mg AttachmentSource 21 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00c486b0-bd7b-4898-834d-8c656e5e73cbFacts
GIVLAARI shares ligands containing GalNAc 3 residues to siRNA for delivery to hepatocellular cells, givosiran molecular weight is 16,300.34 Da, Initial U.S. Approval is 2019.GIVLAARISource 22 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167e663c-11e1-497b-a3fc-951d65d58eaaFacts
PLUVICTO is a radioactive ligand remedy that combines ligands to PSMA with 177Lu via D5 chelate, that the PL weight is 1216.06 g/g, and Initial U.S. Approval is 2022.PLUVICTO23 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1aFacts
The first approval of DOXIL (NDA 050718) is November 17, 1995Drugs@FDASource24 https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=050718Facts
Sun Pharma Doxorubicin Hydrochloride liposome injection (ANDA 203263) must be approved on February 4, 2013.Drugs@FDASource25 https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=203263Facts
The first approval of ONIVYDE (NDA 207793) is October 22, 2015Drugs@FDASource26 https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207793Facts
The first approval of LUPRON DEPOT (NDA 0) is January 26, 1989.Drugs@FDASource27 https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019732Facts
In addition, it is possible to use the same key pathway segment of the lipids to compare the distribution of species using the same key pathway segment of the lipids (Q1) and Q2 (concentration less than ±5%), and to produce the active envelope by ammonium phosphate gradient (mainly 4 processes). The lipid additive is definitively important, and to compare the characteristics of the key species (composition, the state of the sulfate doxorubicin crystal, internal environment, form and the lamera, phase transition, particle diameter distribution, PEG layer thickness, PEG layer thickness, surface potential, and circulation). May 2022FDA Product Guidance (Doxorubicin Hydrochloride Liposome Injection)Source28 https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_050718.pdfFacts
99.3% of tumors, about 142 times of tumors. 0.6% ÷ 0.2% = 3 times. DOXIL's fat total of 15.96 mg, about 8.0 times, PEG fat about 20%, ONIVYDE's fat total of 9.15 mg, about 2.1 times, PEG fat about 1.3%, VYX。 about 4.3 times, ABRAXANE about 9 times, LUPRON DEPOT about 8.8 times, ONCASPAR PEG about 71-3.0 (about 2.5-3.0 times of。). "The material of the transport side is about 2 to 9 times the drug." Approx. 17 years and 2 months from DOXIL’s predecessor approval to the first post-department approval。ulation of this article. 0.7% is the central value of animal experiments and is not human-oriented. No salt. The 。 weight of ONCASPAR is a simple sum of subunit 。 weight and mPEG 。 weight. Not comparing effects and safetyThis paper's description of
Develop products that have increased clinical delivery using active pathways through endothelial cells. FDA-approved active targeted nano carriers have been approved since 2018. Establish patient screening by imaging as a clinical standard procedure.The primary information indicating the establishment and approval was not confirmed at the time of the investigation (September 2026). No active targeting type approval is fully confirmed)Undetermined / Future
Comparison of why active targeting succeeds in connecting ligands to small sThe primary information compared directly to the scope of the survey was not confirmed. The description of the body is the reading (explanation) of this article, and the facts published are the facts.
The DDS technology as a technology for carrying. Nanocarriers were divided into four types. The discussion of the EPR effect was considered as a problem of "reproduction and universality". Read that the cells in the body are a layer of protein. The PEG layer has been used as a dispersion agent and anti-fouling coating. A summary that ligands are effective after reaching the tumor. Read that the medicine is close to solids and reduces leakage. Emission control was divided into three types. Reads "Equivalence of Internal Structure and Interface" that is required for later products. Reads whether the particle production process and the process of ligand can be divided into scale-up. Reads that the source of raw materials becomes the same condition for fat suppliers. Position of the paper.and commentary of this article based on the publication content. It is not the opinion of authors and regulatory authorities of each paper
Measures to evaluate the effectiveness and effect of each product, clinical results and safetyThis article is an explanation of material technology and preparation technology, and does not evaluate and compare the effects and safety of the treatment. Approved products quoted only the composition and approval date listed in the regulatory publication
Fig. 1 - Fig. 4, Fig. 6 - Fig. 8 is a drawing for explanation, not actual。s, particles, tissues, equipment. Hero image and figure 5 are AI generation imagesNotes by this article

Last Updated: September 26, 2026 / Source is limited to primary information (FDA approved documentation, Drugs@FDA, FDA product guidance, reader review paper). They are distinguished from the facts that have been sourced as "instructions" because they contain readings in material and process design. The number of animal experiments (e.g. 0.7%, %ID/g) is not human-oriented. The clinical evaluation of the EPR effect, the status of approval of active targeted nano-carrier, and the establishment of patient sorting by image cannot be confirmed as the final information was not confirmed. This article explains materials technology and preparation technology.It does not evaluate the effectiveness and safety of the treatment, but it is not medical advice. All diagrams are illustrations for explanation. Figure 1, Figure 2, Figure 3, Figure 4, Figure 6, and Figure 8 are vector drawings, and Figure 5 is an AI-generated image.This is not a photo of actual particles, tissues, and products.

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