Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs

• Published in: bioRxiv
• Main Authors: Lim, Chaemin, Ramsey, Jacob D, Hwang, Duhyeong K, Teixeira, Susana Cm, Poon, Chi-Duen, Strauss, Joshua D, Sokolsky, Marina, Kabanov, Alexander V
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.06.2021; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Antineoplastic drugs; Antitumor agents; Breast cancer; Drug delivery; Drug dependence; Micelles; Morphology; Nanotechnology; Pharmaceuticals; Pharmacology and Toxicology; Physicochemical properties; Tumors; polymeric micelle; pharmacokinetics; micelle morphology; critical micelle concentration; tumor accumulation
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2021.06.10.447962

Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and wormlike morphologies. We observed that poly(2 oxazoline) based polymeric micelles can be elongated over time from a spherical structure to wormlike structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; wormlike micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles. Competing Interest Statement AVK is an inventor on patents pertinent to the subject matter of the present contribution and co founder of DelAqua Pharmaceuticals Inc. having intent of commercial development of POx based drug formulations. MSP discloses potential interest in DelAqua Pharmaceuticals Inc. as a spouse of co-founder.