Validation, Optimization and Hepatoprotective Effects of Boeravinone B and Caffeic Acid Compounds from Boerhavia diffusa Linn

Boerhavia diffusa, also known as Punarnava, is a plant of the Nyctaginaceae family that has been utilized in traditional medicine to cure a variety of ailments. The goal of this study was to use response surface methodology (RSM) to optimize the maximum percentage yield of boeravinone B and caffeic acid from Boerhavia diffusa roots, and simultaneous determination of boeravinone B and caffeic acid in newly developed single solvent system and demonstrate the hepatoprotective benefits of boeravinone B and caffeic acid. The extraction process examined extraction time, extraction temperature and solvent concentration, which were optimized via Box–Behnken experimental design. The proposed HPTLC method for the quantification of boeravinone B and caffeic acid were successfully validated and developed. The method was validated in term of linearity and detection limit, quantification limit, range, precision, specificity and accuracy. The separation of boeravinone B and caffeic acid bands was achieved on HPTLC plate using formic acid: ethyl acetate: toluene (1:3:5 v/v) as developing system. Densitometric analyses of boeravinone B and caffeic acid was carried out in the absorbance mode at 254 nm. The maximum percentage yield of caffeic acid and boeravinone B from Boerhavia diffusa require appropriate extraction parameters such as temperature, time, organic solvents and water content, which can be achieved using the Box-Behnken statistical design provide time: temperature: solvent ratio (30:45:40 v/v) for extraction of caffeic acid and 60:60:40 v/v for extraction of boeravinone B. The boeravinone B (200 µg/mL) and caffeic acid (200 µg/mL) showed the most significant hepatoprotective activity compared with standard sylimarin in HepG2 cell induced with galactosamine 40 mM toxicity. The findings supported B. diffusa’s traditional use as a functional food forhuman health benefits

Analysis of prevalence of adverse events connected with anti-tuberculosis drugs during pregnancy: A meta-analysis

Background: Mycobacterium tuberculosis infection is transmitted among humans via airborne droplets. The drugs used in the initial treatment regimen for tuberculosis (TB) cross the placenta, raising some concerns regarding their safety during pregnancy may provide a more valid approach for evaluating the relative influence of various risk factors. Adverse events of anti-tuberculous (anti-TB) drug during pregnancy remain uncertain and controversial issues. Methods: We performed a systematic analysis to study the adverse events connected with anti-TB drugs usage during pregnancy. The risk of bias in the included studies was assessed using the Cochrane Collaboration criteria. Interstudy heterogeneity was assessed via Cochran's test. Assuming heterogeneity, a random-effects model was applied. Outcomes were pooled using the inverse variance method. Besides, a funnel plot was created to assess publication bias. We used Egger's linear regression test of funnel plot asymmetry, modified to accommodate inter-study heterogeneity. Effect estimates and confidence intervals for all studies were depicted on a forest plot. Results: The prevalence of total adverse events for all anti-TB drugs was 25.9 %. According to the drug category, the prevalence of total adverse events was 50 % for ethambutol, 32.6 % for the six-month directly observed treatment short-course (DOTS), 31.4 % for the nine-month DOTS, and 13.7 % for isoniazid. Conclusions: There is a high rate of reported adverse events associated with anti-TB drugs usage during pregnancy. We concluded that more high-quality clinical studies and research works are needed to reach a conclusive decision on the safety of the treatment of TB among pregnant women

Preparation of NLCs-Based Topical Erythromycin Gel: In Vitro Characterization and Antibacterial Assessment

In the present study, erythromycin (EM)-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification and ultra-sonication method. EM-NLCs were optimized by central composite design using the lipid (A), pluronic F127 (B) and sonication time (C) as independent variables. Their effects were evaluated on particle size (Y1) and entrapment efficiency (Y2). The optimized formulation (EM-NLCs-opt) showed a particle size of 169.6 ± 4.8 nm and entrapment efficiency of 81.7 ± 1.4%. EM-NLCs-opt further transformed into an in-situ gel system by using the carbopol 940 and chitosan blend as a gelling agent. The optimized EM-NLCs in situ gel (EM-NLCs-opt-IG4) showed quick gelation and were found to be stable for more than 24 h. EM-NLCs-opt-IG4 showed prolonged drug release compared to EM in situ gel. It also revealed significant high permeation (56.72%) and flux (1.51-fold) than EM in situ gel. The irritation and hydration study results depicted no damage to the goat cornea. HET-CAM results also confirmed its non-irritant potential (zero score). EM-NLCs-opt-IG4 was found to be isotonic and also showed significantly (p < 0.05) higher antimicrobial activity than EM in situ gel. The findings of the study concluded that NLCs laden in situ gel is an alternative delivery of erythromycin for the treatment of bacterial conjunctivitis

Drug Delivery Challenges and Current Progress in Nanocarrier-Based Ocular Therapeutic System

Drug instillation via a topical route is preferred since it is desirable and convenient due to the noninvasive and easy drug access to different segments of the eye for the treatment of ocular ailments. The low dose, rapid onset of action, low or no toxicity to the local tissues, and constrained systemic outreach are more prevalent in this route. The majority of ophthalmic preparations in the market are available as conventional eye drops, which rendered <5% of a drug instilled in the eye. The poor drug availability in ocular tissue may be attributed to the physiological barriers associated with the cornea, conjunctiva, lachrymal drainage, tear turnover, blood–retinal barrier, enzymatic drug degradation, and reflex action, thus impeding deeper drug penetration in the ocular cavity, including the posterior segment. The static barriers in the eye are composed of the sclera, cornea, retina, and blood–retinal barrier, whereas the dynamic barriers, referred to as the conjunctival and choroidal blood flow, tear dilution, and lymphatic clearance, critically impact the bioavailability of drugs. To circumvent such barriers, the rational design of the ocular therapeutic system indeed required enriching the drug holding time and the deeper permeation of the drug, which overall improve the bioavailability of the drug in the ocular tissue. This review provides a brief insight into the structural components of the eye as well as the therapeutic challenges and current developments in the arena of the ocular therapeutic system, based on novel drug delivery systems such as nanomicelles, nanoparticles (NPs), nanosuspensions, liposomes, in situ gel, dendrimers, contact lenses, implants, and microneedles. These nanotechnology platforms generously evolved to overwhelm the troubles associated with the physiological barriers in the ocular route. The controlled-drug-formulation-based strategic approach has considerable potential to enrich drug concentration in a specific area of the eye

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC)

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (−) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of −0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential