Chitosan/Alginate-Based Nanoparticles for Antibacterial Agents Delivery.

Nanoparticle systems integrating alginate and chitosan emerge as a promising avenue to tackle challenges in leveraging the potency of pharmacological active agents. Owing to their intrinsic properties as polysaccharides, alginate and chitosan, exhibit remarkable biocompatibility, rendering them conducive to bodily integration. By downsizing drug particles to the nano-scale, the system enhances drug solubility in aqueous environments by augmenting surface area. Additionally, the system orchestrates extended drug release kinetics, aligning well with the exigencies of chronic drug release requisite for antibacterial therapeutics. A thorough scrutiny of existing literature underscores a wealth of evidence supporting the utilization of the alginate-chitosan nanoparticle system for antibacterial agent delivery. Literature reviews present abundant evidence of the utilization of nanoparticle systems based on a combination of alginate and chitosan for antibacterial agent delivery. Various experiments demonstrate enhanced antibacterial efficacy, including an increase in the inhibitory zone diameter, improvement in the minimum inhibitory concentration, and an enhancement in the bacterial reduction rate. This enhancement in efficacy occurs due to mechanisms involving increased solubility resulting from particle size reduction, prolonged release effects, and enhanced selectivity towards bacterial cell walls, stemming from ionic interactions between positively charged particles and teichoic acid on bacterial cell walls. However, clinical studies remain limited, and there are currently no marketed antibacterial drugs utilizing this system. Hence, expediting clinical efficacy validation is crucial to maximize its benefits promptly.

Alginate and Chitosan-Based Hydrogel Enhance Antibacterial Agent Activity on Topical Application.

Untreated topical infections can become chronic, posing serious health issues. Optimal skin adherence is crucial in addressing such infections. In this context, chitosan and alginate emerge as promising candidates for use as a foundation in the development of topical hydrogels. The aim of this review is to examine the literature on topical hydrogel formulations that use chitosan and alginate as foundations, specifically in the context of topical antibacterial agents. The research methodology involves a literature review by examining articles published in databases such as PubMed, Scopus, ScienceDirect, and Google Scholar. The keywords employed during the research were "Alginate", "Chitosan", "Hydrogel", and "Antibacterial". Chitosan and alginate serve as bases in topical hydrogels to deliver various active ingredients, particularly antibacterial agents, as indicated by the search results. Both have demonstrated significant antibacterial effectiveness, as evidenced by a reduction in bacterial colony counts and an increase in inhibition zones. This strongly supports the idea that chitosan and alginate could be used together to make topical hydrogels that kill bacteria that work well. In conclusion, chitosan and alginate-based hydrogels show great potential in treating bacterial infections on the skin surface. The incorporation of chitosan and alginate into hydrogel formulations aids in retaining antibacterial agents, allowing for their gradual release over an optimal period. Therefore, hydrogels specifically formulated with chitosan and alginate have the potential to serve as a solution to address challenges in the treatment of topical bacterial infections.

Nanosuspension-Based Drug Delivery Systems for Topical Applications.

Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.

Efficacy and safety of casirivimab-imdevimab combination on COVID-19 patients: A systematic review and meta-analysis randomized controlled trial.

Background: The advantages and disadvantages of casirivimab-imdevimab for coronavirus disease 2019 are not well understood. We conducted a systematic review and meta-analysis of relevant literature to determine the therapeutic effectiveness and potential side effects of casirivimab-imdevimab in COVID-19 patients. Methods: Databases were searched from the time of their commencement until February 28th, 2023. The primary results evaluated were the death rate at 28 days, progression of current clinical symptoms within 28 days, viral load, discharge from hospital, and any adverse events. Also, we contrasted the effects of the casirivimab-imdevimab treatment with placebo or standard of care. The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023412835). Results: A total of eight studies were included, comprising 19,819 patients, and conducted a qualitative assessment of their risk of bias using the Cochrane risk of bias tool. Casirivimab-imdevimab effectively reduced the mortality rate (OR = 0.62; 95 % CI of 0.40-0.98; p = 0.04; I2 = 30 %) and reduced the progression of clinical symptoms (OR = 0.86; 95 % CI of 0.79-0.93; p = 0.0003; I2 = 57 %). Casirivimab-imdevimab also improved viral load clearance and hospital discharge. Additionally, the trials' findings demonstrated a slight decrease in the likelihood of adverse events occurring with the use of casirivimab-imdevimab. Conclusion: Our research suggests that casirivimab-imdevimab may be a valuable, safe, and effective anti-SARS-CoV-2 regimen.

Effectiveness of Mesenchymal Stem Cell Secretome on Wound Healing: A Systematic Review and Meta-analysis.

BACKGROUND: Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis on the effectiveness of secretome in promoting wound healing. METHODS: To ensure the rigor and transparency of our study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, as registered in PROSPERO with ID: CRD42023412671. We conducted a comprehensive search on four electronic databases to identify studies evaluating the effect of secretome on various clinical parameters of wound repair. In addition, we evaluated the risk of bias for each study using the Jadad and Newcastle-Ottawa scale. To synthesize the data, we employed a fixed-effects model and calculated the mean difference or odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Based on six included articles, secretome is known to affect several clinical parameters in wound healing included the size and depth of ulcers during healing; the E´chelle d'évaluation clinique des cicatrices d'acne (ECCA) score, epidermal thickness, collagen fibers, abnormal elastic tissues, volume of atrophic acne scars, skin pore volume, and erythema during acne scar healing; and microcrust areas, erythema index, transepidermal water loss, volume of atrophic acne scars, erythema, and relative gene expression of procollagen type I, procollagen type III, and elastin were evaluated in wound healing after laser treatment. Meta-analysis studies showed that secretome reduced ulcer size (mean difference: 0.87, 95% CI of 0.37-1.38, p = 0.0007), decreased ulcer depth (mean difference: 0.18, 95% CI of 0.11-0.25, p < 0.00001), and provided patient satisfaction (odds ratio: 9.71, 95% CI of 3.47-21.17, p < 0.0001). However, secretome failed to reach significance in clinical improvement (OR 0.38, 95% CI 0.10, 1.53, p = 0.06). CONCLUSION: The secretome provides good effectiveness in accelerating wound healing through a mechanism that correlates with several clinical parameters of wound repair.

Propolis-Based Nanostructured Lipid Carriers for α-Mangostin Delivery: Formulation, Characterization, and In Vitro Antioxidant Activity Evaluation.

α-Mangostin (a xanthone derivative found in the pericarp of Garcinia mangostana L.) and propolis extract (which is rich in flavonoids and phenols) are known for their antioxidant properties, making them potential supplements for the treatment of oxidative stress-related conditions. However, these two potential substances have the same primary drawback, which is low solubility in water. The low water solubility of α-mangostin and propolis can be overcome by utilizing nanotechnology approaches. In this study, a propolis-based nanostructured lipid carrier (NLC) system was formulated to enhance the delivery of α-mangostin. The aim of this study was to characterize the formulation and investigate its influence on the antioxidant activity of α-mangostin. The results showed that both unloaded propolis-based NLC (NLC-P) and α-mangostin-loaded propolis-based NLC (NLC-P-α-M) had nanoscale particle sizes (72.7 ± 1.082 nm and 80.3 ± 1.015 nm, respectively), neutral surface zeta potential (ranging between +10 mV and -10 mV), and good particle size distribution (indicated by a polydispersity index of <0.3). The NLC-P-α-M exhibited good entrapment efficiency of 87.972 ± 0.246%. Dissolution testing indicated a ~13-fold increase in the solubility of α-mangostin compared to α-mangostin powder alone. The incorporation into the propolis-based NLC system correlated well with the enhanced antioxidant activity of α-mangostin (p < 0.01) compared to NLC-P and α-mangostin alone. Therefore, the modification of the delivery system by incorporating α-mangostin into the propolis-based NLC overcomes the physicochemical challenges of α-mangostin while enhancing its antioxidant effectiveness.

Potency of Xanthone Derivatives from Garcinia mangostana L. for COVID-19 Treatment through Angiotensin-Converting Enzyme 2 and Main Protease Blockade: A Computational Study.

ACE2 and Mpro in the pathology of SARS-CoV-2 show great potential in developing COVID-19 drugs as therapeutic targets, due to their roles as the "gate" of viral entry and viral reproduction. Of the many potential compounds for ACE2 and Mpro inhibition, α-mangostin is a promising candidate. Unfortunately, the potential of α-mangostin as a secondary metabolite with the anti-SARS-CoV-2 activity is hindered due to its low solubility in water. Other xanthone isolates, which also possess the xanthone core structure like α-mangostin, are predicted to be potential alternatives to α-mangostin in COVID-19 treatment, addressing the low drug-likeness of α-mangostin. This study aims to assess the potential of xanthone derivative compounds in the pericarp of mangosteen (Garcinia mangostana L.) through computational study. The study was conducted through screening activity using molecular docking study, drug-likeness prediction using Lipinski's rule of five filtration, pharmacokinetic and toxicity prediction to evaluate the safety profile, and molecular dynamic study to evaluate the stability of formed interactions. The research results showed that there were 11 compounds with high potential to inhibit ACE2 and 12 compounds to inhibit Mpro. However, only garcinone B, in addition to being indicated as active, also possesses a drug-likeness, pharmacokinetic, and toxicity profile that was suitable. The molecular dynamic study exhibited proper stability interaction between garcinone B with ACE2 and Mpro. Therefore, garcinone B, as a xanthone derivative isolate compound, has promising potential for further study as a COVID-19 treatment as an ACE2 and Mpro inhibitor.

A systematic review: Molecular docking simulation of small molecules as anticancer non-small cell lung carcinoma drug candidates.

Non-small cell lung carcinoma (NSCLC) is a type of lung cancer with the highest prevalence and mortality rate worldwide. Many cases of this type of cancer are overexpression on epidermal growth factor receptor (EGFR). The use of currently available EGFR inhibitors as one of the treatment options for NSCLC still shows various shortcomings, especially the high failure rate of therapy due to resistance. It is important to find NSCLC drug candidates with EGFR inhibitory activity. There are various published articles and it is prominent to draw evidence-based scientific conclusions as a basis of decision-making to select potential compounds for further research. Polymer matrix composites and ScienceDirect are used as a database for article screening. Research using molecular docking method targeted to EGFR with parameters of Gibbs energy and amino acid interactions between ligands and drug targets are included in inclusion criteria. Compounds that achieve docking parameters and have comparable activity to NSCLC guideline drugs are conscientiously ranked. There are only 11 compounds that achieved the docking parameters and had comparable EGFR inhibitory potential. Top-rated compounds include 1,3,5-trisubstituted pyrazoline (3c), 1,3,5-trisubstituted pyrazoline (6c), 1,3,5-trisubstituted pyrazoline (8d), N-(3,4-Dimethylphenyl)-2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g] quinazolin-2-yl) thio] acetamide. The top-rated compounds can be used and considered for further research processes.

In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2.

Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10-30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.