Chitosan-Carrageenan Polyelectrolyte Complex for the Delivery of Protein Drugs

A chitosan-carrageenan polyelectrolyte complex (PEC) was prepared by salt induced impeding of polyplex formation method and was encapsulated with bovine serum albumin (BSA) to study the potential to be tailored to the pH responsive oral delivery of protein drugs. The FTIR spectra showed the successful formation of the PEC under the experimental condition. The release kinetics of BSA from the PEC was studied in the simulated gastrointestinal fluids with and without digestive enzymes. The prepared PEC showed the nature of pH-sensitivity. A typical controlled release of BSA from the PEC (180？μg of BSA from 3？mg of PEC) was obtained in the simulated intestinal fluid (SIF, pH 7.5), which was due to the significant swelling and disintegration of PEC, but little amount of BSA was released (11？μg of BSA from 3？mg of PEC) in the simulated gastric fluid (SGF, pH 1.2), confirming acidic stability of the prepared PEC. The presence of digestive enzymes was found not to affect the response of PEC to ambient pH value, but to speed up the release of BSA from carriers. 1. Introduction With the rapid development in biotechnology and recombinant technology, more and more therapeutic peptides and proteins have been produced as drugs at commercial scale. Among various routes for administrating the drugs, oral route is preferred due to its high levels of patient acceptance and long term compliance [1]. Moreover, the dosage forms can be formulated with relative ease and are manufactured without sterile conditions [2]. However, this delivery route faces ineffectiveness for the peptide and protein drugs because the drugs can be easily hydrolyzed by the extreme acidity in the stomach and proteolytic enzymes in the gastrointestinal (GI) tract. The penetration barrier also prevents them from crossing the intestinal and then basal membranes for entry into the blood [3]. To improve the oral bioavailability from less than 1% to at least 30–50% for a polypeptide drug delivery through the GI tract has attracted intensive research [4]. Polyelectrolyte complexes (PEC) are formed by the ionic interactions as ionically cross-linked networks when two oppositely charged polyelectrolytes bind each other in an aqueous solution [5]. The net charge fixed on the complex, which is an important factor determining the swelling and the induced volume change of the PEC, is affected by pH value of ambient solution due to the variation in the degree of ionization of functional groups [6]. Thus, the nature of highly pH-sensitive swelling brings PEC to the application of oral drug delivery [7, 8] because