Self-assembling methoxypoly(ethylene glycol)-b-poly(carbonate-co-l-lactide) block copolymers for drug delivery

Michael Danquah, Tomoko Fujiwara, Ram I. Mahato

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Bicalutamide is the most widely used non-steroidal antiandrogen for treating early stage prostate cancer, but suffers variable oral absorption due to its limited aqueous solubility. Thus, our objective was to synthesize novel biodegradable copolymers for the systemic micellar delivery of bicalutamide. Flory-Huggins interaction parameter (χFH) was used to assess compatibility between bicalutamide and poly(l-lactide) or poly(carbonate-co-lactide) polymer pairs. Polyethylene glycol-b-poly(carbonate-co-lactide) [PEG-b-P(CB-co-LA)] copolymers were synthesized and characterized by NMR and gel permeation chromatography. These micelles had average diameter of 100 nm and had a smooth surface and distinct spherical shape. Drug loading studies revealed that adding the carbonate monomer could increase bicalutamide loading. Among the series, drug loading of micelles formulated with PEG-b-P(CB-co-LA) copolymer containing 20 mol% carbonate was about four-fold higher than PEG-b-PLLA and aqueous solubility of bicalutamide increased from 5 to 4000 μg/mL. CMC values for PEG-b-P(CB-co-LA) copolymers was up to 10-fold lower than those of PEG-b-PLLA. In vitro release experiments showed PEG-b-P(CB-co-LA) copolymers to be more efficient in sustaining the release of bicalutamide compared to PEG-b-PLLA. Bicalutamide-loaded PEG-b-P(CB-co-LA) micelles showed significant inhibition of LNCaP cell growth in a dose-dependent manner which was similar to the methanol solution of free drug.

Original languageEnglish (US)
Pages (from-to)2358-2370
Number of pages13
JournalBiomaterials
Volume31
Issue number8
DOIs
StatePublished - Mar 1 2010

Fingerprint

Ethylene Glycol
Carbonates
Ethylene glycol
Drug delivery
Polyethylene glycols
Block copolymers
Pharmaceutical Preparations
Micelles
Copolymers
Solubility
Androgen Antagonists
dilactide
bicalutamide
Gel Chromatography
Methanol
Prostatic Neoplasms
Polymers
Gel permeation chromatography
Cell growth
Growth

Keywords

  • Bicalutamide
  • Copolymer
  • Micelles
  • Poly lactic acid
  • Polycarbonate
  • Polyethylene glycol

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Self-assembling methoxypoly(ethylene glycol)-b-poly(carbonate-co-l-lactide) block copolymers for drug delivery. / Danquah, Michael; Fujiwara, Tomoko; Mahato, Ram I.

In: Biomaterials, Vol. 31, No. 8, 01.03.2010, p. 2358-2370.

Research output: Contribution to journalArticle

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