Formulation and characterization of polyester/polycarbonate nanoparticles for delivery of a novel microtubule destabilizing agent

Vaibhav Mundra, Yan Lu, Michael Danquah, Wei Li, Duane D. Miller, Ram I. Mahato

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Since our newly synthesized potent 5-indolyl derivative, (2-(1 H-Indol-5-yl) thiazol-4-yl) 3, 4, 5-trimethoxyphenyl methanone (LY293), to treat resistant melanoma was hydrophobic, our objective was to synthesize a biodegradable copolymer for formulating this drug into nanoparticles and to determine its anticancer activity and mechanism of action. Methods: Methoxy poly (ethylene glycol)-b-poly (carbonate-co-lactide) [mPEG-b-P (CB-co-LA)] was synthesized for formulating LY293 into nanoparticles by o/w emulsification and stabilization by solvent evaporation. Particle size, drug release profile, in vitro efficacy in multiple melanoma cells, and mechanism of action of drug-loaded nanoparticles were determined. Results: LY293-loaded nanoparticles with 170 nm mean size and 2.2 and 4.16% drug loading efficiently inhibited proliferation of A375 and B16F10 cells with IC50 of 12.5 nM and 25 nM, respectively. LY293 circumvented multidrug resistance and inhibited proliferation of Pgp overexpressing MDA-MB435/LCC6 MDR1 melanoma cells. Upon treatment with LY293-loaded nanoparticles, A375 cells underwent cell cycle arrest in G2/M phase and apoptotic cell death. Immunofluorescence images showed inhibition of tubulin polymerization after treatment with LY293. Conclusion: LY293-loaded mPEG-b-P (CB-co-LA) nanoparticles showed excellent efficacy and induced apoptosis in melanoma cells. These polyester/polycarbonate-based nanoparticles provided an excellent platform to deliver different poorly soluble drugs to melanoma.

Original languageEnglish (US)
Pages (from-to)3064-3074
Number of pages11
JournalPharmaceutical Research
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2012

Fingerprint

polycarbonate
Polyesters
Microtubules
Nanoparticles
Melanoma
Pharmaceutical Preparations
Carbonates
Emulsification
Ethylene Glycol
G2 Phase
Multiple Drug Resistance
Cell death
Tubulin
Cell Cycle Checkpoints
Particle Size
Polymerization
Cell Division
Polyethylene glycols
Inhibitory Concentration 50
Fluorescent Antibody Technique

Keywords

  • LY293
  • melanoma
  • polymeric nanoparticles
  • tubulin polymerization

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Formulation and characterization of polyester/polycarbonate nanoparticles for delivery of a novel microtubule destabilizing agent. / Mundra, Vaibhav; Lu, Yan; Danquah, Michael; Li, Wei; Miller, Duane D.; Mahato, Ram I.

In: Pharmaceutical Research, Vol. 29, No. 11, 01.11.2012, p. 3064-3074.

Research output: Contribution to journalArticle

Mundra, Vaibhav ; Lu, Yan ; Danquah, Michael ; Li, Wei ; Miller, Duane D. ; Mahato, Ram I. / Formulation and characterization of polyester/polycarbonate nanoparticles for delivery of a novel microtubule destabilizing agent. In: Pharmaceutical Research. 2012 ; Vol. 29, No. 11. pp. 3064-3074.
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AU - Mahato, Ram I.

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