title: Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules.
abstract: The 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 ± 0.4 μm diameter. Encapsulation efficiency of LbL-MC increased linearly (R(2 )= 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 μM concentration, free IM showed significantly (p < 0.05) 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.
authors: Department of Pharmacy, BITS Pilani, Hyderabad Campus , Shameerpet, Hyderabad 500078, Andhra Pradesh , India.
authors: Praveen K
authors: PK
authors: Mandapalli
authors: Suman
authors: S
authors: Labala
authors: Deekshith
authors: D
authors: Vanamala
authors: Manali P
authors: MP
authors: Koranglekar
authors: Lakshmi A
authors: LA
authors: Sakimalla
authors: Venkata Vamsi K
authors: VV
authors: Venuganti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D002214:Capsules; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D000068877:Imatinib Mesylate; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine; D011137:Polystyrenes; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D002214:Capsules; D010879:Piperazines; D011137:Polystyrenes; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011094:Polyethyleneimine
keywords: Biodistribution; PEGylation; controlled release; imatinib mesylate; polymeric drug carriers