Green Synthesis and Characterization of Silver Nanoparticles of Psidium guajava Leaf Extract and Evaluation for Its Antidiabetic Activity.

Diabetes mellitus (DM) and its complications are a severe public health concern due to the high incidence, morbidity, and mortality rates. The present study aims to synthesize and characterize silver nanoparticles (AgNPs) using the aqueous leaf extract of Psidium guajava (PGE) for investigating its antidiabetic activity. Psidium guajava silver nanoparticles (PGAg NPs) were prepared and characterized by various parameters. The in vivo study was conducted using PGE and PGAg NPs in Streptozotocin (STZ)-induced diabetic rats to assess their antidiabetic properties. STZ of 55 mg/kg was injected to induce diabetes. The PGE, PGAg NPs at a dose of 200 and 400 mg/kg and standard drug Metformin (100 mg/kg) were administered daily to diabetic rats for 21 days through the oral route. Blood glucose level, body weight changes, lipid profiles, and histopathology of the rats' liver and pancreas were examined. In the diabetic rats, PGE and PGAg NPs produced a drastic decrease in the blood glucose level, preventing subsequent weight loss and ameliorating lipid profile parameters. The histopathological findings revealed the improvements in pancreas and liver cells due to the repercussion of PGE and PGAg NPs. A compelling effect was observed in all doses of PGE and PGAg NPs; however, PGAg NPs exhibited a more promising result. Thus, from the results, it is concluded that the synthesized PGAg NPs has potent antidiabetic activity due to its enhanced surface area and smaller particle size of nanoparticles.

Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics.

Sitagliptin (MK-0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

Design and formulation of mucoadhesive microspheres of sitagliptin.

Mucoadhesive microspheres of sitagliptin (SITCM), a new anti-diabetic drug was prepared with carbopol 934 P using Buchi B-90 nano spray drier and optimized to analyse the key effects and relations of three factors on formulation of SITCM were studied. The appearance of the microspheres was found to be shriveled to nearly spherical, with a narrow size of 2-8 µm. The drug loading and percentage yield was found to be 73 ± 0.2% and 92 ± 0.3%, respectively. In vitro release indicated Korsmeyer-Peppas pattern mucoadhesion of SITCM-8 was found to be 7.8 ± 0.3 h. In vivo studies in rats suggest that the sitagliptin was retained in the gastrointestinal tract for an extended period of time (∼12 h) and control group was reduced significantly (∼4 h). This study concludes that the mucoadhesive microsphere could be one of the most appropriate drug delivery approaches for the successful delivery of sitagliptin.

Entrapment of andrographolide in cross-linked alginate pellets: I. Formulation and evaluation of associated release kinetics.

Andrographolide, the 'King of bitters' requires high doses in the form of an extract (33.3%w/w) to be used as a hepatoprotectant. Since a large dose of this herb is known to cause gastric distress, vomiting, loss of appetite and nausea on regurgitation, it was thought of to convert the drug itself into a bitterless micropellet. The technique of ionotropic gelation of sodium alginate with calcium ions with subsequent drug entrapment was employed. The optimization of process parameters like the bore diameter of the needle, % concentration of sodium alginate, method of drying, drying time and temperature, time of contact of the micropellets in calcium chloride solution and concentration of calcium chloride to be used for the gelation were undertaken. The micropellets were finally prepared by adding 2.5%w/v of sodium alginate into a 2%w/v solution of calcium chloride solution using 20-guage flat tip needle and dried using a hot air oven at 60(o)C for 6 hrs. The so formed pellets were completely bitterless and released the andrographolide preferably away from the stomach. Pellets with varied drug: polymer ratio (1:2, 1:1 and 2:1) were prepared accordingly and analyzed for release kinetics. Release studies showed only about 15% release upto 4 hrs in pH 1.2 and pH 4.0 respectively and released the remaining in pH 7.4. The data obtained in the dissolution studies was fitted into various mathematic models defining kinetics of drug release like the zero-order rate equation, first-order rate equation, Hixson-crowell, 2/3rd rule, Korsemeyer-Peppas, Baker-lonsdale, Higuchi, Weibull, Ford and Hopfenberg Equation. The release kinetics of andrographolide from the alginate pellets was found to be best described by the korsemeyer-peppas equation which provided n values ranging from 1.0-1.47 with good linearity of the best-fit line (R(2)=0.9973). In conclusion, andrographolide can be easily converted to bitterless multiple unit dose oral delivery systems with good entrapment efficiency and a maximum release of 86% by utilizing the technique of ionotropic gelation.

Entrapment of andrographolide in cross-linked alginate pellets: II. Physicochemical characterization to study the pelletization of andrographolide.

This paper deals with the characterization of pellets containing andrographolide in two parts. The first part deals with characterization of the pellets to ascertain the identity and integrity of andrographolide. Part two involves characterization of the pellets containing Andrographis paniculata extract (33.3%) prepared in the paper I for their micromeritic properties like Particle size, Particle size distribution, Sphericity measurements like Shape ratio and Aspect ratio, Tapped density, Compressibility index, Hausner's ratio and Angle of repose. In addition, our aim was also to derive information about the mechanism of gelation with entrapment of andrographolide to supplement results obtained about the release mechanisms deduced in paper I. Since this work requires use of techniques like FTIR, FTRaman, MTDSC and XRPD, it was necessary to prepare alginate micropellets using pure andrographolide (99.89%) rather than the multicomponent extract using the same procedure discussed in paper I. The integrity of the drug was maintained in the cross-linked micropellets as was seen in the MTDSC and FTIR spectra supported by the FTRaman spectra. The depolymerisation transitions, the reversing and non-reversing heat flow signals were determined using the MTDSC and interpreted to study the mechanism of pelletization. The MTDSC profiles also confirmed the integrity of the drug by exhibiting a sharp endotherm at 232(o)c that is the melting point of andrographolide. The XRPD spectrum of the micropellets ascertained that the crystallinity of andrographolide was maintained. The relationship of the nature of the drug present in the micropellets related to release mechanisms is discussed. In conclusion, it can be said that andrographolide can be successfully incorporated into cross-linked micropellets of alginate without affecting its integrity or nature to deliver it as a bitterless monoherbal preparation.