Purpose: Irinotecan, a campothecin derivative is used in combination with other chemotherapeutic drugs for treating pancreatic cancer. In this study, we have designed a biodegradable polymeric micelles of irinotecan for controlled drug release with an aim to improve biodistribution
Methods: Poly(ethylene glycol)-block-poly(2- methyl-2-carboxyl-propylene carbonate) (PEG-PCC) was synthesized and characterized by NMR. PEG-PCC was partially modified with hydrophobic L-phenylalanine methyl ester (PME) moieties using carbodiimide coupling. Phenylalanine-modified PEG-b-PCC (PEG-b-PCC-g-PME) based polymeric micelles with ionic cores were prepared by nanoprecipitation method. Micelles prepared by nanoprecipitation were characterized for particle size, zeta potential, drug loading, encapsulation efficiency, in vitro drug release and in vitro cytotoxicity studies.
Results: Synthesis of poly(ethylene glycol)-block-poly(2- methyl-2-carboxyl-propylene carbonate) (PEG-PCC) and its hydrophobic modification was performed and their composition was confirmed by 1H NMR. Irinotecan was successfully encapsulated within the ionic cores of PEG-b-PCC-g-PME with a high drug loading capacity (~20%). Ionic interaction between negatively charged core and positively charged Irinotecan resulted in assembly of nanosized micelles (~130 nm) with uniform size distribution pattern (PDI~0.1). These drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. Micelles showed pH dependent drug release with slow drug release at physiological conditions and significantly faster at pH 5.5 which makes this delivery system suitable for irinotecan delivery to tumor. Drug loaded micelles exhibited a dose-dependent cytotoxicity in MiaPACA cancer cell lines.
Conclusion: Hydrophobically modified micelles with ionic core can be efficiently utilized for encapsulation and pH dependent tumor delivery of irinotecan.
Michael Berna– Manchester College School of Pharmacy
Jerusah Okwoyo– Manchester College School of Pharmacy
Valentin Bogun– Manchester College School of Pharmacy
Vaibhav Mundra– Manchester University, Fort Wayne