Doxycycline Loaded Collagen-Chitosan Composite Scaffold for the Accelerated Healing of Diabetic Wounds.

One major complication of diabetes mellitus is diabetic wounds (DW). The prolonged phase of inflammation in diabetes obstructs the further stages of an injury leading to delayed wound healing. We selected doxycycline (DOX), as a potential drug of choice, due to its anti-bacterial properties along with its reported anti-inflammatory properties. The current study aims to formulate DOX loaded collagen-chitosan non-crosslinked (NCL) & crosslinked (CL) scaffolds and evaluate their healing ability in diabetic conditions. The characterization result of scaffolds reveals that the DOX-CL scaffold holds ideal porosity, a low swelling & degradation rate, and a sustained release of DOX compared to the DOX-NCL scaffold. The in vitro studies reveal that the DOX-CL scaffold was biocompatible and enhanced cell growth compared with CL scaffold treated and control groups. The anti-bacterial studies have shown that the DOX-CL scaffold was more effective than the CL scaffold against the most common bacteria found in DW. Using the streptozotocin and high-fat diet-induced DW model, a significantly (p≤0.05) faster rate of wound contraction in the DOX-CL scaffold treated group was observed compared to those in CL scaffold treated and control groups. The use of the DOX-CL scaffold can prove to be a promising approach for local treatment for DWs.

Implementation of two different experimental designs for screening and optimization of process parameters for metformin-loaded carboxymethyl chitosan formulation.

Metformin (MET) was effectively encapsulated into O-carboxymethyl chitosan (O-CMC) polymeric formulation using an experimental design method. Six factors Plackett-Burman (PB) design was utilized to find the significant process parameters. Linear equations used to study the effect of each process parameters on particle size (PS), encapsulation efficiency (EE), and zeta potential (ZP) and the most influential three factors decided for further optimization. Optimization was carried out by implementing three-factor three-level Box-Behnken (BB) design. Mathematical models were generated by regression analysis for responses of PS, EE, and ZP. Two-step experimental design took into account for the preparation of optimized formulation with maximum %EE (72.78 ± 9.7%) and minimum PS (225.67 ± 5.53 nm) at optimum process conditions with a ZP of -5.22 mV for the nano-polymeric formulation in an economical matter by reduction chemical use and formulation time. Furthermore, the biological activity of the final formulation was determined by in vitro cytotoxicity study compared to free MET. The cytotoxicity result reveals that both pure drug and nano-formulation biocompatible with MCF10A non-tumorigenic cell line and lethal for the MCF7 cell line. These in vitro results were the first helpful step to further investigate O-CMC loaded MET nanoparticles in diagnostic and therapeutic applications of breast cancer.

Formulation and characterization of chitosan encapsulated phytoconstituents of curcumin and rutin nanoparticles.

Curcumin and Rutin are natural polyphenolic molecules exhibits several pharmacological actives like antibacterial, anticancer, antioxidant, chemo-preventive and anti-inflammatory properties. However till date, no studies have been reported on their combination efficacy, especially in treating multi-drug resistance of cancers because of their poor solubility and bioavailability. Hence in the present study, an attempt has been made to load both these drugs into a single nanoparticlulate system to enhance their bioavailability and efficacy. This novel formulation was prepared by solvent evaporation technique and was evaluated for particle size and shape using Zeta Sizer, Scanning Electron Microscopy (SEM) and Fourier Transform Infra Red (FT-IR) Spectroscopy. The optimized formulation was further subjected to in vitro and in vivo evaluations. The prepared nanoparticles were in the size range of 25-100nm and the release profile was found to be Non -Fickian transport. In-vivo pharmacokinetic studies were carried in rabbits and the pharmacokinetic profile was studied. The results indicate that oral bioavailability of Curcumin and Rutin has been increased to 3.06 and 4.24 folds respectively when compared to their pure drugs. This data suggest that the present novel nanoparticles loaded with these combinational drugs may have better therapeutic potential in treating drug resistant cancers.

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-1ß, 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.

Development and validation of simultaneous estimation method for curcumin and piperine by RP-UFLC.

Curcumin and piperine are proven for their potent medicinal benefits to treat various diseases and they are most commonly used combination in various Indian systems of medicine such as Ayurveda, Siddha and Unani. The objective of the present work is to develop a simultaneous estimation of curcumin and piperine by reverse phase Ultra-fast liquid chromatographic (RP-UFLC) method. The chromatographic separation was performed on a C8 column (250 x 4.6 mm, 5µ i.d.) stationary phase using a mobile phase of 25mM potassium dihydrogen ortho phosphate buffer (pH 3.5) and acetonitrile (30: 70 v/v) at a flow rate of lml/min at detection wave length of 280nm. The calibration curve was plotted in the concentration range of 0-2200ng/ml and found to be linear for both curcumin (r(2)=0.996) and piperine (r(2)=0.999). The method was validated for parameters such as accuracy, sensitivity, precision, linearity, specificity, ruggedness and robustness as per ICH guidelines. The developed simple, precise and specific method can be used as a quality control tool for qualitative and quantitative estimation of curcumin and piperine in various food products, herbal medicines and nutraceuticals.