Polymeric Composite Matrix with High Biobased Content as Pharmaceutically Relevant Molecular Encapsulation and Release Platform

• Published in: ACS applied materials & interfaces 2021-09, Vol.13 (34), p.40229-40248
• Main Authors: Hazra, Raj Shankar, Dutta, Debasmita, Mamnoon, Babak, Nair, Gauthami, Knight, Austin, Mallik, Sanku, Ganai, Sabha, Reindl, Katie, Jiang, Long, Quadir, Mohiuddin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and Medical Applications of Materials and Interfaces; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cellulose - chemistry; Delayed-Action Preparations - chemistry; Doxorubicin - chemistry; Doxorubicin - therapeutic use; Drug Liberation; Humans; Mice; Nanoparticles - chemistry; Polyesters - chemistry; Proof of Concept Study; Triple Negative Breast Neoplasms - drug therapy
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c03805

Drug delivery systems (DDS) that can temporally control the rate and extent of release of therapeutically active molecules find applications in many clinical settings, ranging from infection control to cancer therapy. With an aim to design a locally implantable, controlled-release DDS, we demonstrated the feasibility of using cellulose nanocrystal (CNC)-reinforced poly (l-lactic acid) (PLA) composite beads. The performance of the platform was evaluated using doxorubicin (DOX) as a model drug for applications in triple-negative breast cancer. A facile, nonsolvent-induced phase separation (NIPS) method was adopted to form composite beads. We observed that CNC loading within these beads played a critical role in the mechanical stability, porosity, water uptake, diffusion, release, and pharmacological activity of the drug from the delivery system. When loaded with DOX, composite beads significantly controlled the release of the drug in a pH-dependent pattern. For example, PLA/CNC beads containing 37.5 wt % of CNCs showed a biphasic release of DOX, where 41 and 82% of the loaded drug were released at pH 7.4 and pH 5.5, respectively, over 7 days. Drug release followed Korsmeyer’s kinetics, indicating that the release mechanism was mostly diffusion and swelling-controlled. We showed that DOX released from drug-loaded PLA/CNC composite beads locally suppressed the growth and proliferation of triple-negative breast cancer cells, MBA-MB-231, via the apoptotic pathway. The efficacy of the DDS was evaluated in human tissue explants. We envision that such systems will find applications for designing biobased platforms with programmed stability and drug delivery functions.