Amphiphilic PEO-b-PBLG Diblock and PBLG-b-PEO-b-PBLG Triblock Copolymer Based Nanoparticles: Doxorubicin Loading and In Vitro Evaluation

• Published in: Macromolecular bioscience Vol. 15; no. 1; pp. 124 - 137
• Main Authors: Kakkar, Dipti, Mazzaferro, Silvia, Thevenot, Julie, Schatz, Christophe, Bhatt, Anant, Dwarakanath, Bilikere S., Singh, Harpal, Mishra, Anil K., Lecommandoux, Sebastien
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.01.2015; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Biopolymers - chemistry; Block copolymers; Carriers; Chemical Sciences; Click Chemistry; Cycloaddition; Doxorubicin; Drug Carriers - chemistry; Drugs; Flow Cytometry; Fluorescence; In Vitro Techniques; Micelles; Microscopy; Molecular Structure; Nanomedicine - methods; Nanomedicine - trends; nanoparticles; Nanoparticles - chemistry; PBLG; PEO; Polyethylene Glycols - chemistry; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemistry; Polymers; PBLG; click chemistry; block-copolymers; nanoparticles; PEO; POLY(GAMMA-BENZYL L-GLUTAMATE); DRUG-DELIVERY; POLYMERIC MICELLES; ANTITUMOR-ACTIVITY; THERAPEUTIC APPLICATIONS; INTRACELLULAR DELIVERY; ROD-COIL; BIOMEDICAL APPLICATIONS; BLOCK-COPOLYMER; POLY(ETHYLENE OXIDE)
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201400451

Huisgen's 1,3‐dipolar cycloaddition (“Click Chemestry”) has been used to prepare amphiphilic PEO‐b‐PBLG diblock and PBLG‐b‐PEO‐b‐PBLG triblock copolymers as potential carriers of anticancer drugs. Spherical and flower shaped micelles (D ≈100 nm) were obtained from diblock and triblock copolymers respectively. DOX was effectively encapsulated up to 18 wt.% and 50–60% of it was steadily released from the micelles over a period of 7 d. Flow cytometry and fluorescence microscopy confirmed the effective intracellular uptake as well as the sustained release of DOX from micelles. These results suggest that the diblock as well as triblock copolymers are promising carriers for intra‐cellular drug delivery. Huisgen's 1,3‐dipolar cycloaddition is used as a versatile approach to prepare amphiphilic block copolymers of PEO and PBLG, which result in spherical micelles (≈100 nm) capable of successfully entrapping the anticancer drug, doxorubicin. The efficacy of these drug‐loaded micelles toward cellular uptake is proven by flow cytometry and fluorescence microscopy.