Search

Abstract Background Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms. Results The PPL conjugate was successfully synthesized and characterized using FTIR, 1H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension. Conclusion From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy. Graphical Abstract

Abstract Background Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited. Results In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs. To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively. Conclusion This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy. Graphical abstract

Despite various efforts, a successful selective delivery system for chemotherapeutic agents for lung cancer is still lacking. Dry powder inhaler (DPI) systems based on proliposomes (PLMs) could be a potential system for the efficient delivery of paclitaxel to lungs. PLM-based DPI prepared with a freeze-drying method can therefore be an alternative. Paclitaxel-loaded PLM-based DPI (PTX-PLM-DPI) powders were prepared using the method of thin film deposition on a carrier followed by freeze drying. These were prepared using soya phosphatidylcholine (SPC) and cholesterol as the lipids and mannitol as the carrier. The reconstituted liposomes were evaluated in terms of size, morphology, drug entrapment, release and cytotoxicity. The DPI powders were evaluated for their flow property, surface topography, dose uniformity and in vitro lung deposition. Stable and free-flowing PTX-PLM-DPI powder was obtained that could be reconstituted into homogenous liposomal vesicles < 200 nm as confirmed by TEM and SEM studies. The liposomes showed drug entrapment of 92.64 ± 1.4% and diffusion-controlled release of up to 28% in 24 h. These liposomes showed better dose-dependent cytotoxicity in A549 cells in comparison to paclitaxel suspension with IC50 values of 46 ± 0.87 ng/mL and 154.9 ± 3.64 ng/mL, respectively. In vitro lung deposition studies of the PTX-PLM-DPI showed sufficient deposition with the fine particle fraction (FPF) of 50.86 ± 2.8% of particles with an aerodynamic diameter less than 5 µ. Hence, it canbe concluded that PLM-based DPI prepared by freeze drying can be a promising, stable, safe and free-flowing system for the enhanced lung delivery of paclitaxel.

Abstract Background Lakadong turmeric (LKD) from Meghalaya, India, boasts high curcumin levels, but lacks scientific study. Moreover, Curcumin's poor solubility hinders its clinical use in inflammation and wound healing. This study isolated curcumin from LKD, forming a PLGA nanosuspension-based nanogel and explored for its potential anti-inflammatory and cutaneous wound healing activity in Wistar rats. Methodology The LKD rhizome was successively extracted by soxhlet using chloroform, hexane, ethyl acetate and methanol and their total phenolic content and antioxidant property was determined. Chloroform extract was loaded in column chromatography and curcumin was isolated, purified and characterized by FTIR, NMR, DSC, MS and HPTLC and its purity was analyzed by HPLC. The isolated curcumin was loaded into PLGA nanosuspensions by nanoprecipitation method followed by conversion to carbopol based Nanogel. The nanogels were characterized physicochemically and the drug permeation was observed. The optimized nanogel was evaluated for its anti-inflammatory and cutaneous wound healing activity by carrageenan-induced paw edema and excision wound model in albino Wistar rats divided in five groups and treated with plain carbopol gel, marketed turmeric cream and Cur NS nanogel (0.6% w/w equivalent curcumin each). Results Results depicted that the chloroform extract showed the presence of a considerable amount of phenolics with 50-60% yield of curcumin. HPLC analysis depicted that the LKD curcumin had higher purity when compared to standard curcumin. Homogenous curcumin nanosuspensions were obtained with size 150 ± 50 nm and PDI 0.2 ± 0.1. The Cur-NS-nanogel showed satisfactory physical property, drug loading and stability. Ex vivo permeation studies in rats showed controlled permeation with steady state flux of 21.28 ± 0.23 µg/cm2/hr in 24 h. Topical intervention with Cur-NS-nanogel (0.6%) significantly (p

Diabetic Foot Ulcers (DFUs) are a devastating micro-vascular complication of diabetes with an increased prevalence and incidence and high rate of morbidity and mortality. Since antibiotics are frequently used to treat DFU, managing the condition has proven to be extremely challenging and may eventually lead to the development of antibiotic resistance. Scientists from around the world are working to develop an alternative solution to the problem of drug resistance by exploring complementary and alternative medicines that may be obtained from natural sources. Hence, the review aims to comprehensively report the information on the natural treatments and therapy used to manage DFU. All of the information described in the current study was gathered from electronic scientific resources, including Google Scholar, PubMed, Scopus, Science Direct, and Springer Link. Findings from the current review revealed the pre-clinical and clinical utility of 18 medicinal plants, 1 isolated compound, 7 polyherbal formulations including herbal creams, a few micronutrients including vitamins and minerals, insect products such as propolis, honey and, Maggot debridement therapy for the treatment and management of DFU. Natural therapies possess better efficacy, low cost, and shorter duration of treatment when compared with the conventional treatments; hence, all information made available about them is crucial to alter the direction of treatment. Furthermore, the data presented in this review are up to date on the potential efficacy of natural complementary medicines for alleviating DFU problems in in vitro and in vivo tests, as well as clinical studies.

Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.