Synthesis, characterization and mechanistic-insight into the anti-proliferative potential of PLGA-gemcitabine conjugate

Khare, Vaibhav; Kour, Smit; Alam, Noor; Dubey, Ravindra Dharr; Saneja, Ankit; Koul, Mytre; Gupta, Ajai Prakash; Singh, Deepika; Singh, Shashank; Saxena, Ajit Kumar; Gupta, Prem N.

doi:10.1016/j.ijpharm.2014.05.005

Cited by 43 publications

(32 citation statements)

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“…Many efforts have been employed to advance the efficiency of gemcitabine, including nanoparticles 11,12 , liposomes 13,14 , micelles 15,16 , polymer-drug conjugates (Prodrugs) 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of TPGS–gemcitabine prodrug micelles for pancreatic cancer therapy

et al. 2016

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The therapeutic potential of a nucleoside analog, gemcitabine, is severely compromised due to its rapid clearance from systemic circulation by enzymatic degradation into inactive metabolite. In the present investigation, micelles based on polymer-drug conjugate were developed for gemcitabine and investigated for their potential to improve cancer chemotherapy. The tocopherol poly(ethylene glycol) succinate 1000 (TPGS)-Gemcitabine prodrug was synthesized via amide linkage and characterised by analytical methods, including FT-IR, 1 H-NMR, and MALDI-TOF.The micellar formulation of TPGS-Gemcitabine prodrug was developed by self-assembly technique and evaluated for various physicochemical parameters including particle size, polydispersity, morphology, critical micelle concentration and release profile. It was shown observed that gemcitabine present in TPGS-Gemcitabine micelles were resistant to deamination from crude cytidine deaminase. The improved cytotoxicity of the micellar formulation was observed by TPGS-Gemcitabine micelles against pancreatic cancer cells. Further, it was investigated that unlike native gemcitabine, the nucleoside transporters were not required for TPGS-Gem micelles to demonstrate its anticancer potential. These finding revealed that TPGS-Gemcitabine micelles may serve as a promising platform for gemcitabine in order to improve its anticancer efficacy.

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“…Many efforts have been employed to advance the efficiency of gemcitabine, including nanoparticles 11,12 , liposomes 13,14 , micelles 15,16 , polymer-drug conjugates (Prodrugs) 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of TPGS–gemcitabine prodrug micelles for pancreatic cancer therapy

et al. 2016

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“…The presence of amide proton at δ 8.26 confirmed the formation of an amine bond with the pendant carboxyl group of mPEG–PCC, which is in agreement with the literature. 7,36,37 GEM loading in mPEG- b -PCC- g -GEM- g -DC was ~14.8% w/w by integrating and calculating amide protons peak at δ 8.26 (Figure S5). However, 1 H NMR analysis can only confirm the chemical conjugation of GEM to the polymer backbone but cannot predict accurate drug loading.…”

Section: Resultsmentioning

confidence: 99%

EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer

et al. 2015

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The objective of this study was to design GE11 peptide (YHWYGYTPQNVI) linked micelles of poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-gemcitabine-graft-dodecanol (PEG-b-PCC-g-GEM-g-DC) for enhanced stability and target specificity of gemcitabine (GEM) to EGFR-positive pancreatic cancer cells. GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles showed EGFR-dependent enhanced cellular uptake, and cytotoxicity as compared to scrambled peptide HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles and unmodified mPEG-b-PCC-g-GEM-g-DC micelles. Importantly, GE11-linked mixed micelles preferentially accumulated in orthotopic pancreatic tumor and tumor vasculature at 24 h post systemic administration. GE11-linked mixed micelles inhibited orthotopic pancreatic tumor growth compared to HW12-linked mixed micelles, unmodified mPEG-b-PCC-g-GEM-g-DC micelles, and free GEM formulations. Tumor growth inhibition was mediated by apoptosis of tumor cells and endothelial cells as determined by immunohistochemical staining. In summary, GE11-linked mixed micelles is a promising approach to treat EGFR overexpressing cancers.

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“…1) following modification of reported methods [18][19][20]. Carbodiimide cross-linking was achieved using DCC/NHS as catalyst, which mediated the formation of an amide linkage between the terminal carboxylic group of PLGA and free amine group of Boc-DAB.…”

Section: Synthesis Of Poly(lactide-co-glycolide)-diaminobutane Conjugmentioning

confidence: 99%

“…Hydroxamate method was used to determine the degree of PLGA activation, as previously reported [19,20]. This method is based the principle of analysing free NHS released from activated PLGA-NHS.…”

Section: Determination Of Degree Of Plga Activation By Hydroxamate Mementioning

confidence: 99%

Development and Analysis of Functionalized Poly(Lactide- Co-Glycolide)Polymer for Drug Delivery

Chen¹,

Huda²,

Benson³

2017

SOJPPS

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Functionalized polymer molecules are the backbone for formulation of targeted biomolecule delivery systems. We report here an effective method for the chemical synthesis of poly (lactide-co-glycolide)-1,4 diaminobutane (PLGA-DAB) in a controlled manner and an efficient gel permeation chromatography (GPC) method for analysis of functionalized PLGA. The synthetic method is simple, reproducible and the functionalized PLGA can be conjugated with any carboxylic acid-containing ligand and ultimately used for targeted drug delivery. The developed GPC analytical method is accurate, selective, precise and easily adaptable for analysing any other functionalized polymer with an amine group. These techniques provide an important basis for formulation scientists to develop functionalized polymers for targeted nanoparticle drug delivery.

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Synthesis, characterization and mechanistic-insight into the anti-proliferative potential of PLGA-gemcitabine conjugate

Cited by 43 publications

References 50 publications

Synthesis and characterization of TPGS–gemcitabine prodrug micelles for pancreatic cancer therapy

Synthesis and characterization of TPGS–gemcitabine prodrug micelles for pancreatic cancer therapy

EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer

Development and Analysis of Functionalized Poly(Lactide- Co-Glycolide)Polymer for Drug Delivery

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