Mannose-Decorated Solid-Lipid Nanoparticles for Alveolar Macrophage Targeted Delivery of Rifampicin.

Alveolar macrophages play a vital role in a variety of lung diseases, including tuberculosis. Thus, alveolar macrophage targeted anti-tubercular drug delivery through nanocarriers could improve its therapeutic response against tuberculosis. The current study aimed at exploring the efficacy of glyceryl monostearate (GMS)-based solid-lipid nanoparticles (SLNs) and their mannose functionalized forms on the alveolar macrophage targeting ability of an anti-tubercular model drug, rifampicin (Rif). Rif-loaded SLNs were accomplished by the solvent diffusion method. These carriers with unimodal particle size distribution (~170 nm) were further surface-modified with mannose via Schiff-base reaction, leading to slight enhancement of particle diameter and a decline of drug loading capacity. The encapsulated Rif, which was molecularly dispersed within the matrices as indicated by their XRD patterns, was eluted in a sustained manner with an initial burst release effect. The uptake efficiency of mannose-modified SLNs was remarkably higher than that of corresponding native forms on murine macrophage Raw 264.7 cells and human lung adenocarcinoma A549 cells. Eventually, the mannose-modified SLNs showed a greater cytotoxicity on Raw 264.7 and A549 cells relative to their unmodified forms. Overall, our study demonstrated that mannose modification of SLNs had an influence on their uptake by alveolar macrophages, which could provide guidance for the future development of alveolar macrophage targeted nanoformulations.

Ferulic acid-g-tamarind gum/guar gum based in situ gel-forming powders as wound dressings.

The current research endeavour aimed to synthesize ferulic acid grafted tamarind gum/guar gum (FA-g-TG/GG) based powders as wound dressings, which could form in situ gels upon contact with wound exudates. In this context, variable amounts of FA were initially grafted with TG via the Steglich esterification reaction protocol and the resulting conjugates were subsequently amalgamated with GG and lyophilized to produce dry powders (F-1 - -F-3) with average particle size within 5.10-5.54 µm and average angle of repose ∼30°. These powders were structurally characterized with 1H NMR, FTIR, DSC, TGA, XRD and SEM analyses. Pristine TG, FA-g-TG and FA-g-TG/GG powders (F-2) revealed their distinct morphological structures and variable negative zeta potential values (-11.06 mV-25.50 mV). Among various formulation (F-1-F-3), F-2 demonstrated an acceptable powder-to-gel conversion time (within 20 min), suitable water vapour transmission rates (WVTR, 2564.94 ± 32.47 g/m2/day) and excellent water retention abilities and swelling profiles (4559.00 ± 41.57 %) in wound fluid. The powders were cytocompatible and conferred antioxidant activities. The powders also displayed fibroblast cell proliferation, migration and adhesion properties, implying their wound-healing potentials. Thus, the developed in situ gel-forming powders could be employed as promising dressings for wound management.

Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy.

The treatment of chronic respiratory infections caused by biofilm formation are extremely challenging owing to poor drug penetration into the complex biofilm structure and high drug resistance. Local delivery of an antibiotic together with a non-antibiotic adjuvant to the lungs could often enhance the therapeutic responses by targeting different bacterial growth pathways and minimizing drug resistance. In this study, we designed new inhalable dry powders containing ciprofloxacin (CIP) and OligoG (Oli, a low-molecular-weight alginate oligosaccharide impairing the mucoid biofilms by interacting with their cationic ions) to combat respiratory bacterial biofilm infections. The resulting powders were characterized with respect to their morphology, solid-state property, surface chemistry, moisture sorption behavior, and dissolution rate. The aerosol performance and storage stability of the dry powders were also evaluated. The results showed that inhalable dry powders composed of CIP and Oli could be readily accomplished via the wet milling and spray drying process. Upon the storage under 20 ± 2 °C/20 ± 2 % relative humidity (RH) for one month, there was no significant change in the in vitro aerosol performances of the dry powders. In contrast, the dry powders became non-inhalable following the storage at 20 ± 2 °C/53 ± 2 % RH for one month due to the hygroscopic nature of Oli, which could be largely prevented by incorporation of leucine. Collectively, this study suggests that the newly developed co-spray-dried powders composed of CIP and Oli might represent a promising and alternative treatment strategy against respiratory bacterial biofilm infections.

Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery.

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen spongeⓇ on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.