Shashank Mulukutla

Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing.

Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well-known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p<0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti-inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability.

5-Aminosalicylic acid attenuates allergen-induced airway inflammation and oxidative stress in asthma.

Pro-inflammatory cytokines regulate the magnitude of allergic reactions during asthma. Tumor necrosis factor--alpha (TNF-α), interleukin-6 (IL-6) and interleukin-13 (IL-13) play a crucial role in aggravating the inflammatory conditions during allergic asthma. In addition, oxidative stress contributes to the pathogenesis of asthma by altering the physiological condition resulting in the development of status asthmaticus. Anti-inflammatory corticosteroids are being widely used for treating allergic asthma. In the present study 5-aminosalicylic acid (5-ASA), a salicylic acid derivative, was evaluated, in vivo for its potential to suppress TNF-α, IL-6 and IL-13 using ovalbumin (OVA) induced allergic asthma in Balb/C mice. Oral administration of 65, 130 and 195 mg/kg 5-ASA significantly reduced the OVA induced total and differential leucocyte count, TNF-α, IL-6, IL-13, nitrite, nitrate, MDA, MPO and TPL levels in the lung lavage samples. Collectively, these findings suggest that 5-ASA is a potent immunomodulator and suppresses key Th2 cytokines production and oxidative stress in OVA-induced asthma.

Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma

Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients.

Peritoneal Mast Cell Stabilization Potential of Ziziphus Xylopyrus (Retz) Wild Extract in RatMesenteric Model

Objective: To investigate the peritoneal mast cell stabilization activity of Ziziphus xylopyrus extracts. Materials and Methods: Ziziphus Xylopyrus L. (family- Rhamnaceae) stem part was successively extracted with ethanol and aqueous to prepare extract of the plant. The extracts of Ziziphus Xylopyrus (Z. xylopyrus) were evaluated for stabilization of mast cell in rat for the evaluation of Hypersensitivity type I allergic reaction in animal models. The extract of Z. xylopyrus ethanolic and aqueous (1, 10 and 100 μg/ml) was evaluated for peritoneal mast cell stabilization activity in rat mesenteric preparation induced by C 48/80. Result: Preliminary phytochemical analysis revealed the presence of carbohydrates, fixed oil, proteins, alkaloids, glycosides, flavonoids and phenolic compounds. The ethanolic and aqueous extracts of Z. xylopyrus showed dose dependent increase in the number of intact cells when compare with C 48/80 at the concentration of 10 and 100 μg/ml. It virtues further work towards the isolation of phyto constituents from this plant. Conclusion: This finding provides evidence that the Z. xylopyrus inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation. Z. xylopyrus has a potential as allergic anti-asthmatic agent.

Pharmacokinetic and tissue distribution studies of 1,9-pyrazoloanthrone, a c-Jun-N-terminal kinase inhibitor in Wistar rats by a simple and sensitive HPLC method

JNK pathway activates c-Jun(s) which are responsible for cell apoptosis; as a result, inhibitors of JNK pathway have the potential to prevent dopaminergic neurons from death and decrease the loss of dopamine in substantia nigra pars compacta (SNpc). Recent in-vitro studies show that 1,9-pyrazoloanthrone (1,9-P) a potent JNK-3 inhibitor prevents the apoptosis of dopaminergic cells of brain. In the present study we formulated liposomes to increase the bioavailability of 1,9-P in the brain and developed a simple, sensitive and selective high performance liquid chromatographic method and validated for the estimation of 1,9-P in Wistar rat plasma and tissue samples. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and rasagiline as the internal standards. Chromatography was performed on Hibar C18 column with mobile phase of ammonium acetate (10mM, pH 8.0 adjusted with ammonia) and ACN at a flow rate of 1mL/min. The lower limit of quantification of the developed method was found to be 2.0ng/mL and 4.0ng/g in plasma and tissue samples respectively. The liposomes of 1,9-P administered to animals at the dose equivalent to 15mg/kg orally demonstrated remarkable absorption into the systemic circulation with maximum concentration (∼7500ng/mL) within 2.0h. The order of the area under curve was found to be kidney>liver>brain>lungs>spleen>heart. The liposomes of 1,9-P were rapidly taken up into brain and showed a good brain concentration after 2.0h; sustenance up to 4.0h was achieved which is better than 1,9-P solution.