In vitro Studies on Anti-diabetic and Anti-ulcer Potentials of Jatropha gossypifolia (Euphorbiaceae)

Purpose: To evaluate α-glucosidase and α-chymotrypsin enzyme inhibitory activity of Jatropha gossypifolia as a probable remedy for the management of diabetes and ulcer.Methods: Different extracts and fractions of the root, leaf and stem bark of the plant were screened for their α-glucosidase and α-chymotrypsin inhibitory activity using standard in vitro inhibition assays. Acarbose and chymostatin were used as positive control, respectively.Results: n-Butanol and ethyl acetate fraction showed maximum enzyme inhibition for α-glucosidase with 67.93 ± 0.66 and 67.67 ± 0.71 % and half maximal concentration (IC50) of 218.47 ± 0.23 and 213.45 ± 0.12 μg/ml, respectively. Dichloromethane and ethyl acetate leaf fractions exhibited maximum α-chymotrypsin inhibition activity of 85.08 ± 0.38 and 83.87 ± 0.70 %, and IC50 of 133.1 ± 0.68 and 134.5 ± 0.12 μg/ml, respectively, Acarbose exhibited enzyme inhibition activity of 92.14 ± 0.38 % with IC50 of 38.24 ± 0.1 μg/ml, while chymostatin exhibited 93.67 ± 0.38 % enzyme inhibition and IC50 of 8.24 ± 0.11 μg/ml.Conclusion: The presence of bioactive secondary metabolities with enzyme-inhibiting activity lends some support for the traditional use of this plant in the management of diabetes and ulcer. However, further investigation of the plant including identification of its active components is required.Keywords: α-Chymotrypsin, α-Glucosidase, Inhibition, Jatropha gossypifolia, Anti-diabetic, Anti-ulce

Porous and highly responsive polymeric fabricated nanometrices for solubility enhancement of acyclovir; characterization and toxicological evaluation

Solubility is one of the major factors which affects several therapeutic mioeties in terms of their therapeutic efficacy. In the current study, we presented a porous and amorphous nanometrices system for the enhancement of the solubility of acyclovir. The polymeric network was fabricated by crosslinking polyethylene glycol-6000, polycaprolactone, and β-cyclodextrin with methacrylic acid by optimizing free radical polymerization technique using methylene bisacrylamide as a crosslinking agent. The formulated nanometrices were then characterized by zetasizer, FTIR, PXRD, Scanning electron microscopy, Thermogravimetric analysis, swelling, sol-gel fraction, drug loading, stability, solubility, and in-vitro dissolution analysis. Since the formulated system has to be administered orally, therefore to determine the in-vivo biocompatibility, nanometrices were administered orally to experimental animals. SEM images provided a rough and porous structure while PXRD showed an amorphous diffractogram of the unloaded and loaded nanometrices. Moreover, the particle size of the optimum loaded formulation was 25 nm higher than unloaded nanometrices due to the repulsion of the loaded drug. A significant loading of the drug with enhanced solubility and dissolution profiles was observed for the poorly soluble drug. The dissolution profile was quite satisfactory as compared to the marketed brand of drug which depicted that the solubility of the drug has been enhanced. Toxicity study conducted on rabbits confirmed the biocompatibility of the nanometrices. The systematic method of preparation, enhanced solubility and high dissolution profile of the formulated nanometrices may be proved as a promising technique to enhance the solubility of poorly aqueous soluble therapeutic agents

Designing of SiO2 mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: Ex vivo evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression

The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol–gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect

Synthesis and Characterization of Partially Metallic Chromium Hollow Nanospheres: A Step toward the Tuning of Magnetic Property

At present hollow nanostructures have been intensive topics of research due to their superior properties over their solid nano counterparts. In this study uniform size chromium hollow nanospheres were synthesized by polyol method followed by simple corrosion etching using a proper solvent combination strategy. Fourier transform infrared (FTIR) and UV Visible spectroscopy have been applied to follow the conversion of precursor into metal particles and then hollow nanospheres respectively. Particle size and morphology have been characterized by particle size analyzer and Field Emission Scanning Electron microscopy (FE SEM). The crystal structures of chromium species such as CrO2 and Cr2O3 resulted from CrOOH have been determined by X-ray diffraction technique (XRD). X-ray photoelectron spectroscopy (XPS) has been applied to evaluate the surface binding energy of chromium ions. Self arranged hollow nanospheres have shown temperature-dependent magnetization. In this way magnetic property of solid chromium nanospheres has been tuned by converting them into hollow nanospheres.</p

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol

Purpose: The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release. Methods: Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels. Results: The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively). Conclusions: As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT

Toxicological evaluation of xanthan gum based hydrogel formulation in Wistar rats using single dose study

Xanthan gum-based hydrogel formulation FXG3 was prepared by a free radical polymerization technique. To assess safety of FXG3 hydrogel for potential application as new drug delivery system, a single oral dose toxicity study was conducted according to OECD guidelines. Female adult rats of Wistar strain were divided into group A and group B. Group A served as the control and was given 1mL/100 g body weight 0.9% saline. Group B received a dose of 5g/kg body weight of FXG3 hydrogel. Rats were observed continuously for 14 days for clinical signs, and prior to terminal sacrifice, blood samples were taken to assess for haematology and biochemical parameters. Selected organs (heart, liver, lung, kidneys, spleen, and stomach) were removed and examined macroscopically, washed, sliced and stained with haematoxylin-eosin for histopathological investigation. No mortality or any signs of acute toxicity was observed during the observation period. No macroscopic alteration was found in the selected organs. Histopathological examination did not show any pathological changes. Thus, the maximal tolerated dose of FXG3 was calculated to be higher than 5g/kg body weight. It can be concluded that FXG3, a xanthan gum-based hydrogel formulation, was non-toxic after acute oral administration at 5g/kg body weight, and thus may be a promising candidate in controlled drug delivery system

β-cyclodextrin chitosan-based hydrogels with tunable pH-responsive properties for controlled release of acyclovir: design, characterization, safety, and pharmacokinetic evaluation

In this work, series of pH-responsive hydrogels (FMA1–FMA9) were synthesized, characterized, and evaluated as potential carrier for oral delivery of an antiviral drug, acyclovir (ACV). Different proportions of β-cyclodextrin (β-CD), chitosan (CS), methacrylic acid (MAA) and N′ N′-methylenebis-acrylamide (MBA) were used to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy confirmed fabrication of new polymeric network, with successful incorporation of ACV. Scanning electron microscopy (SEM) indicated presence of slightly porous structure. Thermal analysis indicated enhanced thermal stability of polymeric network. Swelling studies were carried out at 37 °C in simulated gastric and intestinal fluids. The drug release data was found best fit to zero-order kinetics. The preliminary investigation of developed hydrogels showed a pH-dependent swelling behavior and drug release pattern. Acute oral toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of Wistar rats. Pharmacokinetic study indicated that developed hydrogels caused a significant increase in oral bioavailability of ACV in rabbit plasma as compared to oral suspension when both were administered at a single oral dose of 20 mg kg−1 bodyweight. Hence, developed hydrogel formulation could be used as potential candidate for controlled drug delivery of an antiviral drug acyclovir

Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63–75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen–Crowell’s kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N’-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N’-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition

pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation

The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin&rsquo;s lymphoma. The Hydrogels were prepared using a polymeric blend of agarose, Pluronic acid, glutaraldehyde, and methacrylic acid. The prepared hydrogels were characterized for drug loading (%), swelling pattern, release behavior, the ingredient&rsquo;s compatibility, structural evaluation, thermal integrity, and toxicity evaluation in rabbits. The new polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 58.65&ndash;75.32%. The developed hydrogels showed significant differences in swelling dynamics and drug release behavior in simulated intestinal fluid (SIF) when compared with simulated gastric fluid (SGF). The drug release was persistent and performed in a controlled manner for up to 24 h. A toxicity study was conducted on white albino rabbits. The developed hydrogels did not show any signs of ocular, skin, or oral toxicity; therefore, these hydrogels can be regarded as safe and potential carriers for controlled drug delivery in biomedical applications