Comparison of Shell-Cross-Linked Micelles with Soft and Glassy Cores as a Drug Delivery Vehicle for Albendazole: Is There a Difference in Performance?

• Published in: Macromolecules Vol. 45; no. 13; pp. 5451 - 5462
• Main Authors: Kim, Yoseop, Liemmawal, Elviana D, Pourgholami, Mohammad H, Morris, David L, Stenzel, Martina H
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.07.2012
• Subjects: albendazole; Applied sciences; Biological and medical sciences; cell lines; composite polymers; crystal structure; differential scanning calorimetry; drug carriers; drugs; encapsulation; Exact sciences and technology; General pharmacology; glass transition temperature; hydrophobicity; inhibitory concentration 50; Medical sciences; micelles; nanoparticles; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; polymerization; Polymers with particular properties; polymethylmethacrylate; Preparation, kinetics, thermodynamics, mechanism and catalysts; shelf life; thermodynamics; Biological properties; Antineoplastic agent; Hydrodynamic radius; Graft copolymer; Asymmetric molecule; Cytotoxicity; Drug carrier; Nanoencapsulation; Amidation; Crosslinked copolymer; Methacrylic acid copolymer; Chain transfer; Ethyl acrylate copolymer; Tumor cell; Release; Amphiphilic polymer; Control release polymer; Crosslinking; Dithioester; Ethylene oxide copolymer; Experimental study; Methyl methacrylate copolymer; Diamine; Monodispersed polymer; Albendazole; Internalization; Preparation; Diblock copolymer; Kinetics; Aqueous solution; Radical copolymerization; Micellar solution
• ISSN: 0024-9297; 1520-5835; 1520-5835
• DOI: 10.1021/ma300644v

The understanding of glass transition temperatures T g in drug and polymer systems is indispensable for drug encapsulation and delivery. Amphiphilic block copolymers consisting a various ratios of poly(methyl methacrylate) (T g = 100 °C) and poly(ethyl acrylate) (T g = −22 °C) as the hydrophobic block have been synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization as drug delivery carrier for albendazole (ABZ). Self-assembled micelles with diameters of ∼25 nm with glassy (PMMA) and soft (PEA) core have been synthesized. Differential scanning calorimetry (DSC) has been used to evaluate crystallinity and miscibility of ABZ with the core-forming polymer. All drug–polymer systems are compatible, but they become less miscible with increasing amount of PMMA. The most noticeable difference was the suppression of the crystallinity of the drug with increasing PEA content, a prerequisite for long shelf life of the drug carrier. Since the different micelles are subject to different thermodynamic stability, shell-cross-linking was carried out. Cell experiments against OVCAR-3 cell lines show a fast and efficient uptake of these nanoparticles. Shell-cross-linked micelles were found to be 2–4 times more efficient against OVCAR-3 cells at low concentrations. In contrast, there was no significant difference in the IC50 value of drug carriers with glassy and soft cores.