Search

Purpose: The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers., Method: Conjugates of Glycyl-glycine and alanyl-alanine of chitosan and trimethyl chitosan (on primary alcohol group of polymer located on carbon 6) were synthesized and nanoparticles containing insulin were prepared for oral delivery. Preparation conditions of nanoparticles were optimized and their performance to enhance the permeability of insulin as well as cytotoxicity of nanoparticles in Caco-2 cell line was evaluated. To evaluate the efficacy of orally administered nanoparticles, nanoparticles with the most permeability enhancing ability were studied in male Wistar rats as animal model by measuring insulin and glucose Serum levels., Result: Structural study of all the conjugates by infrared spectroscopy and nuclear magnetic resonance confirmed the successful formation of the conjugates with the desirable substitution degree. By optimizing preparation conditions, nanoparticles with expected size (157.3-197.7 nm), Zeta potential (24.35-34.37 mV), polydispersity index (0.365-0.512), entrapment efficiency (70.60-86.52%) and loading capacity (30.92-56.81%), proper morphology and desirable release pattern were obtained. Glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan showed 2.5-3.3 folds more effective insulin permeability in Caco-2 cell line than their chitosan counterparts. In animal model, oral administration of glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan demonstrated reasonable increase in Serum insulin level with relative bioavailability of 17.19% and 15.46% for glycyl-glycine and alanyl-alanine conjugate nanoparticles, respectively, and reduction in Serum glucose level compared with trimethyl chitosan nanoparticles (p < 0.05)., Conclusion: It seems that glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan have met the aim of this research work and have been able to orally deliver insulin with more than one mechanism in animal model. Hence, they are promising candidates for further research studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of the present study was to develop insulin nanoparticulate systems by using chitosan (CS), triethylchitosan (TEC) and dimethyl-ethylchitosan (DMEC, a new quaternized derivative of chitosan) for colon delivery. The nanoparticles were prepared by the polyelectrolyte complexation (PEC) method. Particle size distribution, zeta potential and polydispersity index of the nanoparticles were determined using dynamic light scattering technique. Transmission electron microscopy (TEM) was also used to observe the morphology of the nanoparticles. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170-270 nm with spherical morphology and smooth surface structure. The amount of insulin loaded into the nanoparticles was determined by measuring the association efficiency and also the content of insulin in the nanoparticles. Insulin loading was found to be more than 80% for all of the nanoparticles. In vitro release studies showed a small burst effect at the beginning and then a sustained release characteristic for 5h. Ex vivo investigations revealed better insulin transport across the colon membrane of rats for nanoparticles made with quaternized derivatives than those made of chitosan. In vivo studies in rats have showed enhanced colon absorption of insulin by using these nanoparticles compared to free insulin in diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect.

The aim of this study was to improve the aerosolisation behaviour of disodium cromogycate (DSCG), using spray drying technique. The effect of vehicle on the drug particle properties was investigated. L-leucine was selected as a natural antiadherent amino acid to improve the deagglomeration of DSCG particles. Spray dried samples of DSCG alone or with L-leucine were prepared from water and ethanol under the same conditions. The powder properties of the samples were examined by laser diffraction, helium densitometer, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. The in vitro deposition was determined, using an Andersen cascade impactor with a Spinhaler at a flow rate of 60 l/min. An amorphous form of the drug was obtained when water was used. However, crystal transformation of original DSCG in the presence of ethanol during spray drying resulted in production of elongated particles. These particles exhibited improved aerodynamic properties, compared to the amorphous and commercial materials. Significant differences in fine particle fraction were observed using the two vehicles. Co-spray drying of DSCG and L-leucine improved the deposition profiles of the drug. These results indicated that the change in crystal structure of DSCG during spray drying process was susceptible to the nature of the vehicle. A crystalline form of DSCG with good aerodynamic properties was achieved during spray drying process. In addition, the processing of DSCG with L-leucine in a single step using ethanol resulted in an improvement in dispersion properties of the drug particles., (copyright 2004 Elsevier B.V.)

The aim of this study was to evaluate the effect of superporous hydrogel (SPH) and SPH composite (SPHC) as permeation enhancers for peptide drug delivery on Caco-2 cell monolayers. Moreover, the cytotoxic effects of these polymers were also studied using trypan blue test, MTT assay and propidium iodide staining. Transepithelial electrical resistance (TEER) studies revealed that both SPH and SPHC polymers were able to decrease TEER values to about 40% of initial values, indicating the ability of these polymers to open tight junctions. Recovery studies of TEER showed that the effects of polymers on Caco-2 cell monolayers were reversible, indicating viability of the cells after incubation with polymers. Both polymers were able to enhance the transport of the hydrophilic marker 14C-mannitol up to 2.7 and 3.8-fold in comparison to the control group. The cumulative transport of fluorescein isothiocyanate labelled dextrans with a molecular weight of 4400 Da (FD4) and 19600 Da (FD20) was enhanced by SPH and SPHC polymers by opening of tight junctions; however, this enhancement was inversely proportional to the molecular weight of marker compounds. Cytotoxicity studies confirmed that the transport enhancing properties of SPH and SPHC polymers were not caused by damage of the Caco-2 cell monolayers. The cells were able to exclude trypan blue as well as propidium iodide after incubation with SPH and SPHC polymers. MTT assay showed that the number of viable cells was higher than 95% after incubation with SPH and SPHC polymers. This indicates that the mitochondrial metabolic activities of the cells were preserved after application of the polymers.