Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery

• Published in: ACS applied materials & interfaces 2016-07, Vol.8 (28), p.17775-17783
• Main Authors: Fenn, Spencer L, Miao, Tianxin, Scherrer, Ryan M, Floreani, Rachael A
• Format: Article
• Language: English
• Subjects: A549 Cells; Alginates - administration & dosage; Alginates - chemistry; Alginates - pharmacokinetics; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Carcinoma - drug therapy; Carcinoma - metabolism; Carcinoma - pathology; Cell Proliferation - drug effects; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Delivery Systems - methods; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Methacrylates - administration & dosage; Methacrylates - chemistry; Methacrylates - pharmacokinetics; Microspheres
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.6b03245

Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently cross-linked sub-microspheres were formed via exposure to green light, in order to investigate effects of cross-linking on drug release and cell internalization, compared to traditional techniques, such as ultraviolet (UV) light irradiation. Cross-linking was performed using light exposure alone or in combination with ionic cross-linking using calcium chloride (CaCl2). Alg-MA sub-microsphere diameters were between 88 and 617 nm, and ζ-potentials were between −20 and −37 mV. Using human lung epithelial carcinoma cells (A549) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-cross-linked sub-microspheres achieving the highest internalization percentages. While blank (nonloaded) Alg-MA submicrospheres were noncytotoxic to A549 cells, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after 5 days of culture. Photo-cross-linked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment.