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.

Tahtat D ，Mahlous M ，Benamer S ，Khodja AN ，Oussedik-Oumehdi H ，Laraba-Djebari F ... -  《-》

Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system.

Xu Y ，Zhan C ，Fan L ，Wang L ，Zheng H ... -  《INTERNATIONAL JOURNAL OF PHARMACEUTICS》

Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin: in vitro and in vivo assessment.

The objective of present research work was to develop alginate coated chitosan core shell nanoparticles (Alg-CS-NPs) for oral delivery of low molecular weight heparin, enoxaparin. Chitosan nanoparticles (CS-NPs) were synthesized by ionic gelation of chitosan using sodium tripolyphosphate. Core shell nanoparticles were prepared by coating CS-NPs with alginate solution under mild agitation. The Alg-CS-NPs were characterized for surface morphology, surface coating, particle size, polydispersity index, zeta potential, drug loading and entrapment efficiency using SEM, Zeta-sizer, FTIR and DSC techniques. Alginate coating increased the size of optimized chitosan nanoparticles from around 213 nm to about 335 nm as measured by dynamic light scattering in zeta sizer and further confirmed by SEM analysis. The performance of optimized enoxaparin loaded Alg-CS-NPs was evaluated by in vitro drug release studies, in vitro permeation study across intestinal epithelium, in vivo venous thrombosis model, particulate uptake by intestinal epithelium using fluorescence microscopy and pharmacokinetic studies in rats. Coating of alginate over the CS-NPs improved the release profile of enoxaparin from the nanoparticles for successful oral delivery. In vitro permeation studies elucidated that more than 75% enoxaparin permeated across the intestinal epithelium with Alg-CS-NPs. The Alg-CS-NPs significantly increased (p<0.05) the oral bioavailability of enoxaparin in comparison to plain enoxaparin solution as revealed by threefold increase in AUC of plasma drug concentration time curve and around 60% reduction in thrombus formation in rat venous thrombosis model. The core shell Alg-CS-NPs showed promising potential for oral delivery and significantly enhanced the in vivo oral absorption of enoxaparin.

Bagre AP ，Jain K ，Jain NK 《-》

Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin.

The alginate-chitosan microspheres with narrow size distribution were prepared by membrane emulsification technique in combination with ion (Ca(2+)) and polymer (chitosan) solidification. The preparation procedure was observed, and the physical properties (particle size distribution, surface morphology, chitosan distribution, zeta potential) of the microspheres were characterized. Subsequently, the microspheres were employed to load model peptide of insulin. The effect of loading ways on the loading efficiency and immunological activity of insulin were investigated. It was shown that the higher loading efficiency (56.7%) and remarkable activity maintenance (99.4%) were obtained when the insulin was loaded during the chitosan solidification process (Method B). Afterward, the release profile in vitro for the optimal insulin-loaded microspheres was investigated. Under the pH conditions of gastrointestinal environment, only 32% of insulin released during the simulated transit time of drug (2 h in the stomach and 4 h in the intestinal). While under the pH condition of blood environment, insulin release was stable and sustained for a long time (14 days). Furthermore, the chemical stability of insulin released from the microspheres was well preserved after they were treated with the simulated gastric fluid containing pepsin for 2 h. Finally, the blood glucose level of diabetic rats could be effectively reduced and stably kept for a long time (∼60 h) after oral administration of the insulin-loaded alginate-chitosan microspheres. Therefore, the alginate-chitosan microspheres were found to be promising vectors showing a good efficiency in oral administration of protein or peptide drugs.

Zhang Y ，Wei W ，Lv P ，Wang L ，Ma G ... -  《-》

Chitosan oligosaccharide as prospective cross-linking agent for naproxen-loaded Ca-alginate microparticles with improved pH sensitivity.

Čalija B ，Milić J ，Cekić N ，Krajišnik D ，Daniels R ，Savić S ... -  《-》