ABSTRACT
AIM: Assessment of preactivated carboxymethyl cellulose as potential excipient for buccal drug delivery. METHODS: Firstly, carboxymethyl cellulose (CMC) and cysteine (SH) were covalently coupled via amide bond formation to obtain thiolated carboxymethyl cellulose (CMC-SH). Further, preactivated carboxymethyl cellulose (CMC-S-S-MNA) was obtained by preactivation with 2-mercaptonicotinic acid (MNA). Sulforhodamine 101 (SRH101) was used as a model drug for permeation study through buccal mucosa. CMC-S-S-MNA was evaluated with respect to mucoadhesive and permeation enhancing effect and cytotoxicity. RESULTS: Thiolated carboxymethyl cellulose exhibited a total amount of 112.46 ± 0.46 thiol groups. CMC-S-S-MNA exhibited around 50% of preactivated thiol groups. The preactivated polymer showed no toxic effect. Furthermore, compared to unmodified CMC, CMC-S-S-MNA revealed 3.0-fold improved mucoadhesive properties according to the rotating cylinder method and 8.8-fold enhancement in mucoadhesiveness by tensile assay, respectively. CONCLUSION: Preactivated carboxymethyl cellulose fulfills the requirements as potential excipient of being mucoadhesive and permeation enhancing for the buccal drug delivery.
Subject(s)
Carboxymethylcellulose Sodium , Cysteine , Drug Carriers , Excipients , Mouth Mucosa/metabolism , Adhesiveness , Animals , Caco-2 Cells , Carboxymethylcellulose Sodium/administration & dosage , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacology , Cell Survival/drug effects , Coloring Agents/administration & dosage , Coloring Agents/chemistry , Coloring Agents/pharmacology , Cysteine/administration & dosage , Cysteine/chemistry , Cysteine/pharmacology , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacology , Excipients/administration & dosage , Excipients/chemistry , Excipients/pharmacology , Humans , In Vitro Techniques , Rhodamines/administration & dosage , Rhodamines/chemistry , Rhodamines/pharmacology , SwineABSTRACT
AIM: To design a novel preactived carboxymethyl cellulose derivative. METHODS: First, carboxymethyl cellulose (CMC) was chemically modified by amide bond formation between primary amino group of cysteine (CYS) and carboxylic moiety of CMC mediated by carbodiimide. Second, obtained CMCCYS was preactivated with 2,2'-dithiodinicotinic acid. Designed CMC-S-S-MNA was characterized by FT-IR. Furthermore, cytotoxicity was conducted on Caco-2 cell line. Swelling behavior, erosion and release of novel CMC-S-S-MNA were performed compared with thiolated and unmodified cellulose, respectively. RESULTS: CMC-S-S-MNA showed no harmful effect on cells. CMC-S-S-MNA exhibited 2.13-fold higher stability in comparison to unmodified cellulose. Furthermore, preactivated carboxymethyl cellulose-cysteine revealed 1.9-fold controlled released compared with respective unmodified carboxymethyl cellulose. CONCLUSION: Novel preactivated carboxymethyl cellulose represents a versatile excipient for drug delivery.
