ORIGINAL PAPERInfluence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules Praveen K. Mandapalli, Suman Labala, Deekshith Vanamala, Manali P. Koranglekar, Lakshmi A. Sakimalla, and Venkata Vamsi K. Venuganti Department of Pharmacy, BITS Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, Andhra Pradesh, India
AbstractThe objective of this study is to investigate the influence of charge of model small molecules on their encapsulation and release behavior in layer-by-layer microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL-MC. Model molecules with varying charge, anionic -ascorbic acid, cationic -imatinib mesylate (IM) and neutral -5-fluorouracil were encapsulated in LbL-MC. Free and encapsulated LbL-MC were characterized using zetasizer, FTIR spectroscope and differential scanning calorimeter. The influence of IM-loaded LbL-MC on cell viability was studied in B16F10 murine melanoma cells. Furthermore, biodistribution of IM-loaded LbL-MC with and without PEGylation was studied in BALB/c mice. Results showed spherical LbL-MC of 3.0 AE 0.4 mm diameter. Encapsulation efficiency of LbL-MC increased linearly (R 2 ¼ 0.89-0.99) with the increase in solute concentration. Increase in pH from 2 to 6 increased the encapsulation of charged molecules in LbL-MC. Charged molecules showed greater encapsulation efficiency in LbL-MC compared with neutral molecule. In vitro release kinetics showed Fickian and non-Fickian diffusion of small molecules, depending on the nature of molecular interactions with LbL-MC. At 50 mM concentration, free IM showed significantly (p50.05) more cytotoxicity compared with IM-loaded LbL-MC. Biodistribution studies showed that PEGylation of LbL-MC decreased the liver and spleen uptake of IM-encapsulated LbL-MC. In conclusion, LbL-MC can be developed as a potential carrier for small molecules depending on their physical and chemical properties.