Lactic acid- and carbonate-based crosslinked polymeric micelles for drug delivery

Michael Danquah, Tomoko Fujiwara, Ram I. Mahato

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co- lactide-co-5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) [mPEG-b-P(CB-co-LA-co- MAC)] and methoxy poly(ethylene glycol)-b-poly(acryloyl carbonate)-b- poly(carbonate-co-lactide) [mPEG-b-PMAC-b-P(CB-co-LA)] copolymers were synthesized by ring-opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8-diazabicycloundec-7-ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8-1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG114-b-P(CB 8-co-LA35-co-MAC2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG 114-b-PMAC2.5-b-P(CB9-co-LA39) (20.29% ± 0.11%).1H NMR and IR spectroscopy confirmed successful crosslinking (∼70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide-loaded crosslinked micelles were more potent compared to non-crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy.

Original languageEnglish (US)
Pages (from-to)347-362
Number of pages16
JournalJournal of Polymer Science, Part A: Polymer Chemistry
Volume51
Issue number2
DOIs
StatePublished - Jan 15 2013

Fingerprint

Carbonates
Micelles
Lactic acid
Drug delivery
Lactic Acid
Copolymers
Crosslinking
Polyethylene glycols
Chemotherapy
Critical micelle concentration
Ring opening polymerization
Cell proliferation
Polydispersity
Free radical polymerization
Light transmission
Encapsulation
Pharmaceutical Preparations
Light scattering
Nuclear magnetic resonance spectroscopy
Dilution

Keywords

  • biomaterials
  • core-crosslinked micelles
  • drug delivery systems
  • interface-crosslinked micelles
  • micelles
  • poly lactic acid
  • polycarbonate

ASJC Scopus subject areas

  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

Cite this

Lactic acid- and carbonate-based crosslinked polymeric micelles for drug delivery. / Danquah, Michael; Fujiwara, Tomoko; Mahato, Ram I.

In: Journal of Polymer Science, Part A: Polymer Chemistry, Vol. 51, No. 2, 15.01.2013, p. 347-362.

Research output: Contribution to journalArticle

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abstract = "Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co- lactide-co-5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) [mPEG-b-P(CB-co-LA-co- MAC)] and methoxy poly(ethylene glycol)-b-poly(acryloyl carbonate)-b- poly(carbonate-co-lactide) [mPEG-b-PMAC-b-P(CB-co-LA)] copolymers were synthesized by ring-opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8-diazabicycloundec-7-ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8-1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG114-b-P(CB 8-co-LA35-co-MAC2.5) had a higher drug encapsulation efficiency (78.72{\%} ± 0.15{\%}) compared to mPEG 114-b-PMAC2.5-b-P(CB9-co-LA39) (20.29{\%} ± 0.11{\%}).1H NMR and IR spectroscopy confirmed successful crosslinking (∼70{\%}) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide-loaded crosslinked micelles were more potent compared to non-crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy.",
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N2 - Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co- lactide-co-5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) [mPEG-b-P(CB-co-LA-co- MAC)] and methoxy poly(ethylene glycol)-b-poly(acryloyl carbonate)-b- poly(carbonate-co-lactide) [mPEG-b-PMAC-b-P(CB-co-LA)] copolymers were synthesized by ring-opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8-diazabicycloundec-7-ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8-1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG114-b-P(CB 8-co-LA35-co-MAC2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG 114-b-PMAC2.5-b-P(CB9-co-LA39) (20.29% ± 0.11%).1H NMR and IR spectroscopy confirmed successful crosslinking (∼70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide-loaded crosslinked micelles were more potent compared to non-crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy.

AB - Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co- lactide-co-5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) [mPEG-b-P(CB-co-LA-co- MAC)] and methoxy poly(ethylene glycol)-b-poly(acryloyl carbonate)-b- poly(carbonate-co-lactide) [mPEG-b-PMAC-b-P(CB-co-LA)] copolymers were synthesized by ring-opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8-diazabicycloundec-7-ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8-1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG114-b-P(CB 8-co-LA35-co-MAC2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG 114-b-PMAC2.5-b-P(CB9-co-LA39) (20.29% ± 0.11%).1H NMR and IR spectroscopy confirmed successful crosslinking (∼70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide-loaded crosslinked micelles were more potent compared to non-crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy.

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KW - interface-crosslinked micelles

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KW - poly lactic acid

KW - polycarbonate

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