Polyelectrolyte Complex of Carboxymethyl Starch and Chitosan as Protein Carrier: Oral Administration of Ovalbumin

Abstract

A novel carboxymethyl starch (CMS)/chitosan polyelectrolyte complex (PEC) was proposed as an excipient for oral administration of ovalbumin. The dissolution of ovalbumin from monolithic tablets (200 mg, 2.1 × 9.6 mm, 50% loading) obtained by direct compression was studied. When CMS was used as an excipient, more than 70% of the loaded ovalbumin remained undigested after 1 h of incubation in simulated gastric fluid (SGF) with pepsin. The complete dissolution, after transfer of tablets into simulated intestinal fluid (SIF) with pancreatin, occurred within a total time of about 6 h. Higher protection (more than 90% stability in SGF) and longer dissolution (more than 13 h) were obtained with 50% CMS/50% chitosan physical mixture or with PEC excipients. A lower proportion of chitosan was needed for PEC than for the CMS/chitosan mixture to obtain a similar dissolution profile. The high protection against digestion by pepsin, the various release times and the mucoadhesion properties of these excipients based on CMS favor the development of suitable carriers for oral vaccinations.

Carboxymethyl starch/alginate microspheres containing diamine oxidase for intestinal targeting

“…CMS was synthesized in aqueous medium from high amylose starch as previously described . Briefly, 40 g of starch was dispersed in 100 mL of distilled water under continuous stirring in a jacketed beaker at 55 °C.…”

“…The degree of substitution of CMS (DS 0.20) was determined by back titration as described by Assaad et al. .…”

Chitosan-based polyelectrolyte complexes as pharmaceutical excipients

“…This PEC performs better than carboxymethyl starch in sustained drug release, as shown by recent studies (Assaad et al, 2011(Assaad et al, , 2012. When used as an excipient in matrix tablets, the PEC was able to provide longer release time than carboxymethyl starch for small molecules (acetaminophen, aspirin) and for ovalbumin, a model of protein drugs.…”

“…For instance, it is supposed to be more favorable for achieving colon drug delivery because chitosan ionically cross-linked with other polymers is less soluble than chitosan in acidic gastric solutions and the anionic polysaccharide is less soluble in neutral intestinal aqueous solutions when cross-linked with chitosan (Assaad et al, 2011(Assaad et al, , 2012. When used as excipients, the PEC presents many advantages over chitosan or the anionic polymer forming a complex with chitosan.…”

The concept of self-assembling and the interactions involved

“…In the intestinal lumen, the carboxylic groups are ionized and they can easily associate with the amino groups of chitosan in a type of click ionic association with CM-Starch:chitosan (Assaad et al, 2012), currently known as polyelectrolyte complexation (PEC). They are protonated and more compact in gastric acidity and are deprotonated and ionized in neutral pH values in the intestinal tract, leading to hydration, erosion, and accelerated release.…”