Doxil® — The first FDA-approved nano-drug: Lessons learned

Barenholz, Yechezkel

doi:10.1016/j.jconrel.2012.03.020

Cited by 3,474 publications

(2,527 citation statements)

References 89 publications

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“…For example, FDA approved Doxil ® , which encapsulate 10,000 doxorubicin drug molecules in single 100 nm sized liposome as a result of the increased drug solubility, allowing for high drug doses, and at the same time minimizing the side effect of cardiotoxicity. [104] However, high doxorubicin loaded in liposomes was achieve beyond the solubility limit, thus most of them are in a solid phase. It was suggested that more than 98% of the circulating drug remaining inside the liposomes after systemic administration due to the presence of cholesterol in the liposomal formulation that contributed to the enhanced drug stability.…”

Section: Cancer Nanomedicine From the Pharmaceutical Perspectivementioning

confidence: 99%

“…For example, PK of the Doxil ® has high AUC, long t 1/2 , and low Cl with relatively small volume of distribution than the free drug. [104] A much longer t 1/2 of Doxil than the free drug may be due to the low release rate, thus eventhough the cardiotoxicity of doxorubicin is reduced, the prolonged tissue retention induces other side effects like foot and hand syndrome. [114] Also, Doxil ® (liposomal doxorubicin) and DaunoXome ® (liposomal daunorubicin), basically share a similar formulation form (liposomes), but the former one contains PEG coating to avoid the MPS and to stabilize the lipid drug encapsulation, and where the free drug can merely be released within extracellular environment; nevertheless, the latter one has a totally different design strategy, aiming at promoting the uptake by the MPS, followed by providing a reservoir from which the free drug can the enter the circulation, thereby DaunoXome ® does not have PEGylation.…”

Section: Pharmacokinetics Of Nanomedicinesmentioning

confidence: 99%

“…For example, passively targeted PEGylated liposomes (Doxil ® ) nanomedicines have demonstrated to be an efficient nanocarrier with high drug loading to deliver the doxorubicin with enhanced tumor accumulation. [104] However, a modest anticancer activity was observed due to low drug release rate in both circulation and tumor resulting in only about 40-50% bioavailability of Doxil ® in the tumor. [114,117] In another clinical studies, liposomal cisplatin formulation (SPI-077) shown a substantial tumor accumulation with almost no anticancer activity due to diffusional limitation of cisplatin through the intact liposomal membrane.…”

Section: Controlled Drug Releasementioning

confidence: 99%

See 2 more Smart Citations

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Section: Cancer Nanomedicine From the Pharmaceutical Perspectivementioning

confidence: 99%

Section: Pharmacokinetics Of Nanomedicinesmentioning

confidence: 99%

Section: Controlled Drug Releasementioning

confidence: 99%

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Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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“…Maruyama et al also reported a similar effect using large unilamellar liposomes with a size about 200 nm [115]. DOX-encapsulated liposomes showed enhanced tumor distribution through enhanced permeability and retention effects [116] and reduced adverse effects of DOX, especially cardiac toxicity [98,117]. A DOX-encapsulated PEGylated liposome formulation (Doxil ® ) was approved by the US Food and Drug Administration in 1995.…”

Section: Overcoming the Rapid Clearance Of Liposomesmentioning

confidence: 99%

“…A DOX-encapsulated PEGylated liposome formulation (Doxil ® ) was approved by the US Food and Drug Administration in 1995. Recently, the development of Doxil ® was reviewed by Barenholz et al [98].…”

Section: Overcoming the Rapid Clearance Of Liposomesmentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

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Regulating Nanomedicine at the Food and Drug Administration

Paradise¹

2019

AMA Journal of Ethics

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The US Food and Drug Administration (FDA) oversees safety and efficacy of a broad spectrum of medical products (ie, drugs, biologics, and devices) under the auspices of federal legislation and agency regulations and policy. Complex and emerging nanoscale products challenge this regulatory framework and illuminate its shortcomings for combination products that integrate multiple mechanisms of therapeutic action. This article surveys current FDA regulatory structures and nanotechnologyspecific guidance, discusses relevant nanomedicine products, and identifies regulatory challenges. Regulatory Demands of NanotechnologyNanotechnology is research and technology development on the nanoscale (traditionally 100 nanometers (nm) or less, or one billionth of a meter) at which particles have novel properties and functions because of their size. 1 At this size, materials exhibit quantum effects, impacting fluorescence, conductivity, magnetic permeability, melting point, and reactivity. 1 The ability to control atoms and molecules at the nanoscale has significantly advanced medical science and catalyzed the field of nanomedicine, defined by the National Institutes of Health as a "highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve." 2 Nanomedicine also includes nanotechnology applications for "diagnosis, monitoring, and control of biological systems." 3 Cutting-edge nanomedicine applications often integrate chemical, mechanical, and biological properties to enable and enhance detection, diagnostic capabilities, and therapeutic modes of action. In the near future, it will be possible for a single nanomedicine product, once deployed in a patient's body, to be programmed to target specific organs and tissues, create images, measure vital signs, diagnose in real time, and subsequently provide tailored therapeutics.

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Doxil® — The first FDA-approved nano-drug: Lessons learned

Cited by 3,474 publications

References 89 publications

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Glycosylation-mediated targeting of carriers

Regulating Nanomedicine at the Food and Drug Administration

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