Gemcitabine-loaded innovative nanocarriers vs GEMZAR: Biodistribution, pharmacokinetic features and<i>in vivo</i>antitumor activity

Celia, Christian; Cosco, Donato; Paolino, Donatella; Fresta, Massimo

doi:10.1517/17425247.2011.632630

Cited by 53 publications

(37 citation statements)

References 98 publications

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“…Examples of beneficial pharmacodynamic effects mediated by liposomes are more elusive to identify; alterations of PD would manifest themselves following careful analysis and accounting for PK effects on drug biodistribution at the organismal, tissue, and cellular levels. It is likely that the source of most apparent changes in PD, such as an increase in potency of an encapsulated drug relative to the unencapsulated drug, actually arise from biodistributional (PK) effects such as demonstrated for the gemcitabine-loaded innovative nanocarrier formulation [27]…”

Section: Introductionmentioning

confidence: 99%

Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

2014

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Liposomal formulations of anticancer agents have been developed to prolong drug circulating lifetime, enhance anti-tumor efficacy by increasing tumor drug deposition, and reduce drug toxicity by avoiding critical normal tissues. Despite the clinical approval of numerous liposome-based chemotherapeutics, challenges remain in the development and clinical deployment of micro- and nano-particulate formulations, as well as combining these novel agents with conventional drugs and standard-of-care therapies. Factors requiring optimization include control of drug biodistribution, release rates of the encapsulated drug, and uptake by target cells. Quantitative mathematical modeling of formulation performance can provide an important tool for understanding drug transport, uptake, and disposition processes, as well as their role in therapeutic outcomes. This review identifies several relevant pharmacokinetic/pharmacodynamic models that incorporate key physical, biochemical, and physiological processes involved in delivery of oncology drugs by liposomal formulations. They capture observed data, lend insight into factors determining overall antitumor response, and in some cases, predict conditions for optimizing chemotherapy combinations that include nanoparticulate drug carriers.

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Section: Introductionmentioning

confidence: 99%

Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

2014

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“…[3] Hydrophobic anchors,s uch as butyl derivatives, conjugated to the PAHy backbone structure, promoted the self-assembly of the biopolymers to pre-formulated liposomes and formed long circulating nanocarriers, similar to PEGylated liposomes. The backbone structure of PAHy can be modified by amino hydrazine groups, thus creatingm acromolecules that improve the biopharmaceuticalf eatureso fS VAs.…”

Section: Resultsmentioning

confidence: 58%

“…The backbone structure of PAHy can be modified by amino hydrazine groups, thus creatingm acromolecules that improve the biopharmaceuticalf eatureso fS VAs. [3] Hydrophobic anchors,s uch as butyl derivatives, conjugated to the PAHy backbone structure, promoted the self-assembly of the biopolymers to pre-formulated liposomes and formed long circulating nanocarriers, similar to PEGylated liposomes. [14] The butyl residue anchored the native PAHy copolymers to the lipid bilayer and formed stable nanoconstructs.…”

Section: Physicochemical Characterizationmentioning

confidence: 99%

“…In recent last years, innovative biopolymers and colloidaln anoparticles, such as liposomes, weres elf-assembled to synthesize an ew generation of supramolecular vesicular aggregates (SVAs), which can be used in pharmaceutics [1,2] and nanomedi-cines. [3,4] Liposome/polymer-basedS VAsp rovides everala dvantages over conventional vesicular and polymericn anoparticles. In particular,t hesei nnovative nanoconstructs show the main advantages of biocompatible polymers, for example, linear and/or branched polymers with several appended groups that can be easily activatedt hrough aq uick reactiont oc onjugate severalt argeted molecules, [5] and liposomes, which are safe, biodegradable, biocompatible, and capable of co-delivering drugs with different physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] Recently,w es ynthesized innovative SVAs made from a,bpoly(aspartyl hydrazide)( PAHy) to deliver chemotherapeutics and investigated their biopharmaceutical features to achieve suitable nanoformulationsf or potential clinicalt reatment. [1][2][3] In particular, PAHy copolymer, aw ater-soluble, biocompatible, nontoxic,a nd non-antigenic polymer (previously used to synthesize therapeutic micelles, [9] innovative scaffoldsf or tissue engineering, [10] polycationic complexes for gene delivery [11] and zwitterionic polypeptide nanogels [12] )w as self-assembled in pre-formulated liposomes by its hydrophobic butyric moieties (PAHy-C 4 )t of orm SVAs. The butyric residue anchored copolymers to the phospholipidb ilayer and exposed the hydrophilic chains towardt he externala queous environment.…”

Section: Introductionmentioning

confidence: 99%

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Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy

et al. 2016

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The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of GEM-loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (A549) and colorectal cancer (CaCo-2) cells. GEM-loaded cationic SVAs increased the anticancer activity in A549 and CaCo-2 cells relative to free drug, neutral SVAs, and CLs. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.

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High‐Load Gemcitabine Inorganic–Organic Hybrid Nanoparticles as an Image‐Guided Tumor‐Selective Drug‐Delivery System to Treat Pancreatic Cancer

Ischyropoulou,

Sabljo,

Schneider

et al. 2023

Advanced Materials

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Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis without effective treatment options. Thus, there is an urgent need for more effective and safe therapies. Here, we present inorganic‐organic hybrid nanoparticles (GMP‐IOH‐NPs) as novel drug‐delivery system for the selective delivery of extraordinarily high concentrations of gemcitabine monophosphate (GMP) not only to the primary tumor but also to metastatic sites. GMP‐IOH‐NPs have a composition [ZrO]2+[GMP]2– with GMP as drug anion (76% of total IOH‐NP mass). Multiscale fluorescence imaging confirms an efficient uptake in tumor cells, independent of the activity of the human‐equilibrative‐nucleoside transporter (hENT1), being responsible for gemcitabine (GEM) transport into cells and a key factor for GEM resistance. Delivering already phosphorylated GMP via GMP‐IOH‐NPs into tumor cells also allows to overcome cellular resistance induced by the down‐regulation of deoxycytidine kinase. GMP‐IOH‐NPs show high accumulation in tumor lesions and only minor liver trapping when given intraperitoneally. GMP‐IOH‐NPs result in a higher anti‐tumor efficacy compared to free GEM and is further enhanced applying cetuximab‐functionalized GMP‐CTX‐IOH‐NPs. By maximizing the therapeutic benefits with high drug load, tumor‐specific delivery, minimizing undesired side effects, overcoming mechanisms of chemoresistance, and preventing systemic GEM inactivation, we anticipate GMP‐IOH‐NPs to have a high chance to significantly improve current PDAC‐patient outcome.This article is protected by copyright. All rights reserved

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Gemcitabine-loaded innovative nanocarriers vs GEMZAR: Biodistribution, pharmacokinetic features andin vivoantitumor activity

Cited by 53 publications

References 98 publications

Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy

High‐Load Gemcitabine Inorganic–Organic Hybrid Nanoparticles as an Image‐Guided Tumor‐Selective Drug‐Delivery System to Treat Pancreatic Cancer

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