Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment.

The study aims for development of an efficient polymeric carrier for evaluating pharmaceutical potentialities in modulating the drug profile of quercetin (QUE) in anti-diabetic research. Alginate and succinyl chitosan are focused in this investigation for encapsulating quercetin into core-shell nanoparticles through ionic cross linking. The FT-IR, XRD, NMR, SEM, TEM, drug entrapment and loading efficiency are commenced to examine the efficacy of the prepared nanoparticles in successful quercetin delivery. Obtained results showed the minimum particle size of ∼91.58nm and ∼95% quercetin encapsulation efficiently of the particles with significant pH sensitivity. Kinetics of drug release suggested self-sustained QUE release following the non-fickian trend. A pronounced hypoglycaemic effect and efficient maintenance of glucose homeostasis was evident in diabetic rat after peroral delivery of these quercetin nanoparticles in comparison to free oral quercetin. This suggests the fabrication of an efficient carrier of oral quercetin for diabetes treatment.

Alginate coated chitosan core-shell nanoparticles for efficient oral delivery of naringenin in diabetic animals-An in vitro and in vivo approach.

The chemical synthesis of this study targets for development of a bio-safe polymeric nano-vehicle for improvising the solubility of the flavanone naringenin in antidiabetic animal study. Nanoparticles were prepared from two cost-effective carbohydrate biopolymers - chitosan and alginate for successful encapsulation of naringenin. Dual crosslinked nanoparticles were synthesized by using Na2SO4 and CaCl2 as crosslinkers. The nanoparticles were characterized by DLS, FTIR, XRD and SEM. The prepared nano-formulations exhibited significant naringenin entrapment of >90% and pH-responsive slow and sustained release of the flavonoid. In-vivo studies revealed significant hypoglycemic effect after oral delivery of the nanoparticles to streptozotocin-induced diabetic rats. Histopathology and several blood parameters indicated that oral administrations of nanoparticles were free from toxicity. Other studies also suggested that polymeric formulations were quite effective for oral delivery of the flavonoid as a therapeutic agent in the treatment of dyslipidemia, hyperglycemia and haemoglobin iron-mediated oxidative stress in type 1 diabetic model.

pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery.

Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

BACKGROUND: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. METHODOLOGY/PRINCIPAL FINDINGS: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. CONCLUSIONS/SIGNIFICANCE: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery.

pH sensitive PAA/S-chitosan hydrogel was prepared using ammonium persulfate (APS) as an initiator and methylenebisacrylamide (MBA) as a crosslinker for oral insulin delivery. The synthesized copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) study; morphology was observed under scanning electron microscope (SEM). The PAA/S-chitosan with ∼ 38% of insulin loading efficiency (LE) and ∼ 76% of insulin encapsulation efficiency (EE), showed excellent pH sensitivity, retaining ∼ 26% of encapsulated insulin in acidic stomach pH 1.2 and releasing of ∼ 98% of insulin in the intestine (pH 7.4), providing a prolonged attachment with the intestinal tissue. The oral administration of insulin loaded PAA/S-chitosan hydrogel was successful in lowering the blood glucose level of diabetic mice. The bioavailability of insulin was ∼ 4.43%. Furthermore, no lethality or toxicity was documented after its peroral administration. Thus, PAA/S-chitosan hydrogel could serve as a promising oral insulin carrier in future.

Oral insulin delivery by self-assembled chitosan nanoparticles: in vitro and in vivo studies in diabetic animal model.

We have developed self-assembled chitosan/insulin nanoparticles for successful oral insulin delivery. The main purpose of our study is to prepare chitosan/insulin nanoparticles by self-assembly method, to characterize them and to evaluate their efficiency in vivo diabetic model. The size and morphology of the nanoparticles were analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The average particle size ranged from 200 to 550 nm, with almost spherical or sub spherical shape. An average insulin encapsulation within the nanoparticles was ~85%. In vitro release study showed that the nanoparticles were also efficient in retaining good amount of insulin in simulated gastric condition, while significant amount of insulin release was noticed in simulated intestinal condition. The oral administrations of chitosan/insulin nanoparticles were effective in lowering the blood glucose level of alloxan-induced diabetic mice. Thus, self-assembled chitosan/insulin nanoparticles show promising effects as potential insulin carrier system in animal models.