Dual responsive magnetic composite nanogels for thermo-chemotherapy.

With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204W/g for the concentration of 2mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.

Thermoresponsive polymeric gel as an on-demand transdermal drug delivery system for pain management.

The main aim of this work is to design a heat triggered transdermal drug delivery system (TDDS) using a thermoresponsive polymer, poly (N-vinyl caprolactam) [PNVCL] based gel, where in patients can themselves administer a pulse of drug on mere application of heat pad over the TDDS, whenever pain is experienced. The phase transition temperature of PNVCL was tuned to 35 °C by grafting it onto a pH sensitive biopolymer, Chitosan, to synthesize Chitosan-g-PNVCL (CP) co-polymer which render the gel both thermo- and pH-responsive property. The application of triggered delivery was explored by loading acetamidophenol (a model hydrophilic drug) and etoricoxib (a model hydrophobic drug). In vitro drug release experiments were performed at three different temperatures (25, 32 and 39 °C) at two different pH (5.5 and 7) to study its drug release with response to temperature and pH. Drug release profiles obtained were found to have enhanced release for both the drugs respectively at 39 °C (above LCST) and pH5.5 when compared to other release conditions. In vitro skin permeation of both the drugs performed in rat abdominal skin using Franz diffusion cell showed enhanced drug release when the skin was subjected to higher temperature (39 °C). Moreover, it was also found that skin permeation for hydrophobic drug was better than that of hydrophilic drug. The in vivo biocompatibility studies of the CP gel in rat skin proved that the gel is biocompatible. The results obtained demonstrated the potential use of the thermoresponsive CP gel as an on-demand localized drug delivery system.

Poly (caprolactone) microparticles and chitosan thermogels based injectable formulation of etoricoxib for the potential treatment of osteoarthritis.

This study aimed to evaluate Poly (caprolactone) microparticles (MPs) loaded composite injectable Chitosan gel (CICGs) as a dual purpose (visco-supplement and intra articular drug delivery depot) therapeutic agent for the treatment of Osteoarthritis. Etoricoxib (COX-2 inhibitor), a highly hydrophobic drug was chosen as a model drug for the study. When administered orally, Etoricoxib poses severe cardiovascular toxicity issues. So, we have attempted to deliver this drug intra-articularly, which could retain the drug longer in the joint region and thus could ameliorate these toxicity issues. CICGs were prepared by dispersing MPs in the chitosan-Ammonium hydrogen phosphate solution and incubated at 37 °C. Rheology studies proved that gels were stable and had visco-elastic properties comparable to that of existing visco-supplements. The in vitro drug release profiles of CICGs were found to be more controlled when compared to MPs and bare chitosan gel (BCGs). In vitro and in vivo biocompatibility studies proved that the gels were biocompatible. In vivo synovial drug clearance studies proved that CICGs had a better drug retention capacity than BCGs and MPs. In vivo fluorescence imaging results confirmed that CICGs could stay longer in the joint region when compared to BCGs and MPs. Thus this novel CICGs could be a potential dual purpose gel for the treatment of diseased joint regions especially for Osteoarthritis.

Synthesis, characterizations, in vitro and in vivo evaluation of Etoricoxib-loaded Poly (Caprolactone) microparticles--a potential Intra-articular drug delivery system for the treatment of Osteoarthritis.

Intra-articular Drug delivery systems (IA-DDS) deliver the drug directly to the diseased joint space with significantly lowered systemic toxicities. In this work, we explored Etoricoxib (COX-2 inhibitor)-loaded Poly caprolactone (PCL) microparticles (MPs) as a potential IA-DDS. MPs were prepared by Oil/Water (O/W) emulsion-solvent evaporation method. Formulation parameters like polymer to drug ratio, stabilizer concentration were optimized to get the maximum encapsulation efficiency. The prepared particles were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction studies (XRD), and Differential Scanning Calorimetry (DSC). The particles were found to be spherical and smooth-surfaced using SEM. FTIR studies proved that there was no chemical interaction between the drug and the polymer. XRD and DSC studies confirmed that Etoricoxib existed in its amorphous form while PCL had retained its semi-crystalline phase during the micro-encapsulation process. In vitro drug release studies proved that there was controlled release of the drug from the MPs for nearly 28 days. In vivo synovial drug clearance studies on SD rats proved that drug leach out rate from the joint region to the systemic circulation was slow which indicated that MPs had a good drug retention capacity. In vivo fluorescence imaging results confirmed that MPs could stay longer in the joint region for almost a month. Thus, PCL microparticles could be a potential IA-DDS for the treatment of the diseased joint regions especially for Osteoarthritis.

Development and validation of language evaluation scale Trivandrum for children aged 0-3 years--LEST (0-3).

OBJECTIVE: To develop and validate a simple screening tool which can be used in the Community to identify delay in language development among children of 0-3 years of age. METHODS: The normal range for the 33 items of Language Evaluation Scale Trivandrum for 0-3years LEST(0-3) were carefully selected from various existing language development charts and scales, by experts keeping in mind the face validity and content validity. The criterion validity was assessed using a community sample of 643 children of 0 to 3 years of age, including 340 (52.9%) boys. LEST (0-3) was validated against Receptive Expressive Energent Language Scale, for screening delay in language development among children of 0-3 years. RESULTS: When one item delay was taken as LEST delay (test positive), the sensitivity and specificity of LEST(0-3), was found to be 95.85% and 77.5%, respectively with a negative predictive value of 99.8% and LR (negative) of 0.05.When two item delay was taken as LEST delay(test positive), the sensitivity and specificity of LEST(0-3), was found to be 66.7% and 94.8% respectively with a negative predictive value of 98.7% and LR (negative) of 0.35. The test-retest and inter-rater reliability were good and acceptable (Inter-class correlation of 0.69 for test-retest and 0.94 for inter-rater). CONCLUSIONS: LEST (0-3) is a simple, reliable and valid screening tool for use in the community to identify children between 0-3 years with delay in language development, enabling early intervention practices.

Efficacy of tetracycline encapsulated O-carboxymethyl chitosan nanoparticles against intracellular infections of Staphylococcus aureus.

Intracellular bacterial infections are recurrent, persistent and are difficult to treat because of poor penetration and limited availability of antibiotics within macrophages and epithelial cells. We developed biocompatible, 200 nm sized tetracycline encapsulated O-carboxymethyl chitosan nanoparticles (Tet-O-CMC Nps) via ionic gelation for its sustained delivery of Tet into cells. S. aureus binds and aggregates with Tet-O-CMC Nps increasing drug concentrations at the infection site. Tet-O-CMC Nps were sixfold more effective in killing intracellular S. aureus compared to Tet alone in HEK-293 and differentiated THP1 macrophage cells proving it to be an efficient nanomedicine to treat intracellular S. aureus infections.