The synergistic effect of gamma irradiation and alkaline soaking at low temperature on the pre-deacetylation of α-chitin: Optimization by design of experiment.

The effect of gamma irradiation and alkaline soaking time at low temperature (4 °C) as a pretreatment of α-chitin before its N-deacetylation and the effect temperature, NaOH concentration and the reaction time traditionally used during the deacetylation process were studied by applying a factorial experimental design. The top and bottom levels applied for each factor were 1-25 kGy for γ irradiation dose, 2-18 hours for alkaline soaking time at low temperature (4 °C), 50-85 °C for temperature, 35-60% for NaOH concentration and 30-90 min for reaction time. The measured response of deacetylation degree (DD) was determined by FTIR. The pre-treated samples of α-chitin were characterized by X-ray diffraction, DSC and SEM to investigate physical and chemical modification. The obtained results showed that γ irradiation and alkaline soaking time at low temperature are significant factors. The most influential factor was the temperature during the deacetylation process. The equation of the predictive mathematical model for the DD was obtained as follows: DD(%)=-80.4825+0.4984A[NaOH]+1.1355AT°+0.1505Atime-0.1808ADose+0.9845Asoaktime X-ray diffraction, DSC and SEM revealed that the pre-treatment of α-chitin affected greatly its crystallinity and led to chemical and physical modification of its structure. The pretreatment consisting of γ irradiation and soaking time at 4 °C in alkaline medium played a synergistic effect during the deacetylation process.

Oral delivery of insulin from alginate/chitosan crosslinked by glutaraldehyde.

Insulin is mainly administered via subcutaneous route by injection which is the cause of painful and possible infections. Oral insulin administration would present a more convenient form of application because it is less invasive. Oral delivery of insulin to the gastrointestinal tract is one of the most challenging issues, because it numerous barriers to overcome in order to create an effective system for insulin delivery. In the present study, insulin-loaded alginate/chitosan blend gel beads were prepared with different mass ratios. Chitosan was depolymerized by gamma irradiation at a dose of 80 kGy reducing its molecular weight for ideal blend with sodium alginate. The homogeneous solution of alginate and chitosan was dripped into CaCl2 solution (2%), the resultant calcium crosslinked beads were dipped in glutaraldehyde (2%) solution sequentially to prepare dual crosslinked beads with improved mechanical properties so as to withstand the simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Morphological structure, FTIR analysis, thermogravimetry analysis, specific surface area, gel fraction, swelling kinetics in SGF and SIF, loading efficiency, insulin release behavior, mucoadhesivity of the alginate/chitosan beads were investigated. The cumulative insulin release of pure alginate beads (10:0) reached as maximum level 100% in 3h after they were dipped in SIF. Concerning the beads Alg/Chi (8:2), Alg/Chi (7:3) and Alg/Chi (6:4) the cumulative release of insulin reached 90.5%, 89.2% and 70.2%, respectively in 6h. The rate of 100% was reached after 24h for Alg/Chi (8:2), Alg/Chi (7:3) and after 73 h for Alg/Chi (6:4). The presence of chitosan in the blend beads decreased the cumulative insulin release in gastric media and enhanced behavior of alginate/chitosan beads in intestinal medium due to the crosslinking. The alginate/chitosan beads crosslinked by glutaraldehyde may be considered as potential insulin carriers for oral drug delivery system.