Live attenuated Mycobacterium bovis (M. bovis), marketed as Bacille Calmette-Guérin is the only FDA-approved vaccine against tuberculosis. The prerequisite of cold chain storage between 2 and 8 °C hinders the global vaccination effort. The study aims to investigate the effect of trehalose, sucrose and glycerol combinations in enhancing the stability of M. bovis. The bacilli were formulated in various ratios of trehalose-glycerol, sucrose-glycerol, trehalose-sucrose-glycerol systems (test samples) and sodium glutamate (control), freeze-dried and stored for 28 days at 4 °C, 25 °C and 37 °C. Bacteria viability at pre-, post-freeze-drying and after storage were quantified by its density in colony-forming unit per milliliter (CFU/mL) as obtained through the pour plate method. Formulations were characterized using differential scanning calorimetry. Structural collapsed cakes were found on all freeze-dried formulations because of the low Tg'. Comparing between binary and ternary formulations, trehalose-sucrose-glycerol was found to be a superior lyoprotectant. Upon storage, the viability of bacteria in disaccharide-polyol formulations was highest when stored at 4 °C followed by 25 °C. The lowest viability was found after storage at 37 °C. While the ternary disaccharide-polyol system may be used as a thermoprotectant up to 25 °C, sodium glutamate has a superior thermoprotective effect at temperature above 25 °C.
In order to prevent common hypersensitivity reactions to paclitaxel injections (Taxol), we previously reported an ionic liquid-mediated paclitaxel (IL-PTX) formulation with small particle size and narrow size distribution. The preliminary work showed high PTX solubility in the IL, and the formulation demonstrated similar antitumor activity to Taxol, while inducing a smaller hypersensitivity effect in in vitro cell experiments. In this study, the stability of the IL-PTX formulation was monitored by quantitative HPLC analysis, which showed that IL-PTX was more stable at 4 °C than at room temperature. The in vivo study showed that the IL-PTX formulation could be used in a therapeutic application as a biocompatible component of a drug delivery system. To assess the in-vivo biocompatibility, IL or IL-mediated formulations were administered intravenously by maintaining physiological buffered conditions (neutral pH and isotonic salt concentration). From in vivo pharmacokinetics data, the IL-PTX formulation was found to have a similar systemic circulation time and slower elimination rate compared to cremophor EL mediated paclitaxel (CrEL-PTX). Furthermore, in vivo antitumor and hypersensitivity experiments in C57BL/6 mice revealed that IL-PTX had similar antitumor activity to CrEL-PTX, but a significantly smaller hypersensitivity effect compared with CrEL-PTX. Therefore, the IL-mediated formulation has potential to be an effective and safe drug delivery system for PTX.
The management of chronic nonhealing ulcers pose a great challenge because they are associated with morbidity and increased costs. This report presents the observations of standard management along with application of modified collagen with glycerin (MCG) in the periwound area for management of nonhealing wounds. This observational report included 50 patients (33 male, 17 female) aged 24 to 94 years having nonhealing wounds. All wounds were treated using standard treatment protocols (TIME concept), whereas the periwound severity was assessed using the Harikrishna Periwound Skin Classification (HPSC). All patients received once-daily application of MCG lotion directly in the periwound areas and compression bandaging until there was complete wound healing. Patient compliance was ensured by regular follow-up and counseling. All diabetic patients were counseled to ensure glycemic control during the entire follow-up period. The criteria used for wound healing were based on clinical observation, and proper epithelialization of the wound was the end point. The median age of the wounds was 12.0 weeks (95% CI = 8.00 - 58.08). Majority of the non-healing wounds were diabetic foot ulcers with age of wound between 4 weeks to 15 years. The median time to complete wound healing was 12.71 (95% CI = 10.00-16.67) weeks. Standard treatment protocol of TIME principle with periwound area assessment based on HPSC 2015 and treatment accordingly with topical application of MCG along with additional measures has shown complete healing of nonhealing wounds. However, further large-scale comparative studies are needed to substantiate these effects on a larger population.