Development and evaluation of quercetin enriched bentonite-reinforced starch-gelatin based bioplastic with antimicrobial property.

Nowadays novel bio-based materials have been widely employed in food and pharmaceutical industry because of their wide acceptability by the consumers rather than the synthetic materials nevertheless, they possess poor mechanical properties. Reinforcement of biopolymers with intercalation of mineral clays can improve their physicochemical properties; so that such biocomposites possess superior barrier and mechanical properties as well as stability and drug loading efficacy. Thus, this research aimed at formulating quercetin loaded bentonite-reinforced starch-gelatin based novel bioplastic with diverse applicability. The methodology of the study included Box Behnken optimization as well as physical, structural, mechanical and antimicrobial properties evaluation of the proposed reinforced bioplastics. Amount of starch, bentonite and glycerin were the independent variables while the tensile strength, swelling index and elongation percentage were studied as dependent variables. The optimized bioplastic film showed excellent physicochemical and morphological characteristics and also for efficient percentage drug content. The antimicrobial activity showed the highest activity against Escherichia coli followed by Pseudomonas aeruginosa and Staphylococcus aureus. Scanning electron microscopy (SEM) revealed the non-homogenous nature of the film. Generally, the results revealed that quercetin loaded bentonite-reinforced starch-gelatin based could be used as ecological friendly active food packaging as well as pharmaceutical application with significant antimicrobial properties.

Hepatoprotective effects of bioactive compounds from traditional herb Tulsi (Ocimum sanctum Linn) against galactosamine-induced hepatotoxicity in rats.

Ocimum sanctum L. (Tulsi; Family: libiaceae), also known as "The Queen of herbs" or "Holy Basil," is an omnipresent, multipurpose plant that has been used in folk medicine of many countries as a remedy against several pathological conditions, including anticancer, antidiabetic, cardio-protective, antispasmodic, diaphoretic, and adaptogenic actions. This study aims to assess O. sanctum L.'s hepatoprotective potential against galactosamine-induced toxicity, as well as investigate bioactive compounds in each extract and identify serum metabolites. The extraction of O. sanctum L as per Ayurveda was simultaneously standardized and quantified for biochemical markers: rutin, ellagic acid, kaempferol, caffeic acid, quercetin, and epicatechin by HPTLC. Hepatotoxicity was induced albino adult rats by intra-peritoneal injection of galactosamine (400 mg/kg). The quantified hydroalcoholic and alcoholic extract of O. sanctum L (100 and 200 mg/kg body weight/day) were compared for evaluation of hepatoprotective potential, which were assessed in terms of reduction in histological damage, change in serum enzymes such as AST, ALT, ALP and increase TBARS. Twenty chemical constituents of serum metabolites of O. sanctum were identified and characterized based on matching recorded mass spectra by GC-MS with those obtained from the library-Wiley/NIST. We evaluated the hepatoprotective activity of various fractions of hydroalcoholic extracts based on the polarity and investigated the activity at each phase (hexane, chloroform, and ethyl acetate) in vitro to determine how they affected the toxicity of CCL4 (40 mM) toward Chang liver cells. The ethyl acetate fraction of the selected plants had a higher hepatoprotective activity than the other fractions, so it was used in vacuum liquid chromatography (VLC). The ethyl acetate fraction contains high amounts of rutin (0.34% w/w), ellagic acid (2.32% w/w), kaempferol (0.017% w/w), caffeic acid (0.005% w/w), quercetin (0.038% w/w), and epicatechin (0.057% w/w) which are responsible for hepatoprotection. In comparison to standard silymarin, isolated bioactive molecules displayed the most significant hepatoprotective activity in Chang liver cells treated to CCl4 toxicity. The significant high hepatoprotection provided by standard silymarin ranged from 77.6% at 100 µg/ml to 83.95% at 200 µg/ml, purified ellagic acid ranged from 70% at 100 µg/ml to 81.33% at 200 µg/ml, purified rutin ranged from 63.4% at 100 µg/ml to 76.34% at 200 µg/ml purified quercetin ranged from 54.33% at 100 µg/ml to 60.64% at 200 µg/ml, purified epicatechin ranged from 53.22% at 100 µg/ml to 65.6% at 200 µg/ml, and purified kaempferol ranged from 52.17% at 100 µg/ml to 60.34% at 200 µg/ml. These findings suggest that the bioactive compounds in O. sanctum L. have significant protective effects against galactosamine-induced hepatotoxicity.

Physical, Chemical, Barrier, and Antioxidant Properties of Pectin/Collagen Hydrogel-Based Films Enriched with Melissa officinalis.

The essential oil extracted from Melissa officinalis (MOEO) exhibits a wide range of therapeutic properties, including antioxidant, antibacterial, and antifungal activities. The current research aimed to analyze the mechanical, barrier, chemical, and antioxidant properties of pectin and collagen-based films. Hydrogel-based films loaded with varying concentrations of MOEO (0.1%, 0.15%, and 0.2%) were prepared by solvent-casting method, and their physicochemical as well as antioxidant properties were examined. GC-MS analysis revealed the presence of major components in MOEO such as 2,6-octadienal, 3,7-dimethyl, citral, caryophyllene, geranyl acetate, caryophyllene oxide, citronellal, and linalool. Fourier transform infrared (FTIR) results revealed the interaction between components of the essential oil and polymer matrix. Scanning electron microscopy (SEM) revealed that films loaded with the highest concentration (0.2%) of MOEO showed more homogeneous structure with fewer particles, cracks, and pores as compared to control film sample. MOEO-incorporated films exhibited higher elongation at break (EAB) (30.24-36.29%) and thickness (0.068-0.073 mm); however, they displayed lower tensile strength (TS) (3.48-1.25 MPa) and transparency (87.30-82.80%). MOEO-loaded films demonstrated superior barrier properties against water vapors. According to the results, the incorporation of MOEO into pectin-collagen composite hydrogel-based films resulted in higher antioxidant properties, indicating that MOEO has the potential to be used in active food packaging material for potential applications.

Fabrication, Characterization, and Antioxidant Potential of Sodium Alginate/Acacia Gum Hydrogel-Based Films Loaded with Cinnamon Essential Oil.

Several studies have reported the advantages of incorporating essential oils in hydrogel-based films for improving their physiochemical and antioxidant attributes. Cinnamon essential oil (CEO) has great potential in industrial and medicinal applications as an antimicrobial and antioxidant agent. The present study aimed to develop sodium alginate (SA) and acacia gum (AG) hydrogel-based films loaded with CEO. Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), and texture analysis (TA) were performed to analyze the structural, crystalline, chemical, thermal, and mechanical behaviour of the edible films that were loaded with CEO. Moreover, the transparency, thickness, barrier, thermal, and color parameters of the prepared hydrogel-based films loaded with CEO were also assessed. The study revealed that as the concentration of oil in the films was raised, the thickness and elongation at break (EAB) increased, while transparency, tensile strength (TS), water vapor permeability (WVP), and moisture content (MC) decreased. As the concentration of CEO increased, the hydrogel-based films demonstrated a significant improvement in their antioxidant properties. Incorporating CEO into the SA-AG composite edible films presents a promising strategy for producing hydrogel-based films with the potential to serve as food packaging materials.

Three-Dimensional In Vitro Cell Culture Models for Efficient Drug Discovery: Progress So Far and Future Prospects.

Despite tremendous advancements in technologies and resources, drug discovery still remains a tedious and expensive process. Though most cells are cultured using 2D monolayer cultures, due to lack of specificity, biochemical incompatibility, and cell-to-cell/matrix communications, they often lag behind in the race of modern drug discovery. There exists compelling evidence that 3D cell culture models are quite promising and advantageous in mimicking in vivo conditions. It is anticipated that these 3D cell culture methods will bridge the translation of data from 2D cell culture to animal models. Although 3D technologies have been adopted widely these days, they still have certain challenges associated with them, such as the maintenance of a micro-tissue environment similar to in vivo models and a lack of reproducibility. However, newer 3D cell culture models are able to bypass these issues to a maximum extent. This review summarizes the basic principles of 3D cell culture approaches and emphasizes different 3D techniques such as hydrogels, spheroids, microfluidic devices, organoids, and 3D bioprinting methods. Besides the progress made so far in 3D cell culture systems, the article emphasizes the various challenges associated with these models and their potential role in drug repositioning, including perspectives from the COVID-19 pandemic.

Progress in Polymeric Micelles for Drug Delivery Applications.

Polymeric micelles (PMs) have made significant progress in drug delivery applications. A robust core-shell structure, kinetic stability and the inherent ability to solubilize hydrophobic drugs are the highlights of PMs. This review presents the recent advances and understandings of PMs with a focus on the latest drug delivery applications. The types, methods of preparation and characterization of PMs are described along with their applications in oral, parenteral, transdermal, intranasal and other drug delivery systems. The applications of PMs for tumor-targeted delivery have been provided special attention. The safety, quality and stability of PMs in relation to drug delivery are also provided. In addition, advanced polymeric systems and special PMs are also reviewed. The in vitro and in vivo stability assessment of PMs and recent understandings in this area are provided. The patented PMs and clinical trials on PMs for drug delivery applications are considered indicators of their tremendous future applications. Overall, PMs can help overcome many unresolved issues in drug delivery.

Thermosensitive Hydrogels Loaded with Resveratrol Nanoemulsion: Formulation Optimization by Central Composite Design and Evaluation in MCF-7 Human Breast Cancer Cell Lines.

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

Merging Experimental Design and Nanotechnology for the Development of Optimized Simvastatin Spanlastics: A Promising Combined Strategy for Augmenting the Suppression of Various Human Cancer Cells.

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent this challenge, the researchers directed towards the field of nanotechnology to benefit from the nano-size of the formulation in passively targeting the tumor cells. Thus, our study aimed at investigating the potential of a combined mixture-process variable design for optimization of SMV spanlastics (SMV-SPNs) with minimized particle size and maximized zeta potential to enhance the anticancer activity of the drug. The study investigated the effects of Span® 20 and Tween® 80 as mixture components and sonication time as a process variable on particle size, polydispersity index, and zeta potential as responses. SPNs were prepared using an ethanol injection method. Combining the predicted optimized variables' levels is supposed to achieve the set goals with a desirability of 0.821. The optimized spanlastics exhibited a measured globule size of 128.50 nm, PDI of 0.329, and ZP of -29.11 mV. The percentage relative error between predicted responses and the observed ones were less than 5% for the three responses, indicating the optimization technique credibility. A significant improvement in the cytotoxicity of the optimized formulation against three different cancerous cell lines was observed in comparison with SMV. The inhibitory concentration (IC50) values of MCF-7, HCT-116, and HEPG2 were found to be 0.89, 0.39, and 0.06 µM at 24 h incubation. The enhanced cytotoxicity could be assigned to the possible improved permeation and preferential build-up within the cancerous cells by virtue of the minimized size. These findings imply that SMV-SPNs could be an ideal strategy to combat cancer.

Amalgamation of solid dispersion and melt adsorption techniques for augmentation of oral bioavailability of novel anticoagulant rivaroxaban.

The objective of the present study was to evaluate the potential of solid dispersion adsorbate (SDA) to improve the solubility and bioavailability of rivaroxaban (RXN). SDA of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were the amount of carrier (X1) and amount of adsorbent (X2). The responses measured were the time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of the crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbent significantly (P < 0.05) influence both dependent variables. Post-compression data signifies that the compressibility behavior of prepared tablets was within the official standard limits. A significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (> 85% in 10 min) as compared to the pure drug, marketed product, and directly compressible tablet. Cytotoxicity studies confirmed the nontoxicity of prepared RXN SDA tablets. RXN SDA tablets exhibited 2.79- and 1.85-fold higher AUC in comparison to RXN suspension and Xarelto tablets respectively indicating improved oral bioavailability. Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets in comparison to RXN suspension further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.

Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies.

This study aimsto optimize, characterize, and assess the phytosterol-loaded surface-tailored bioactive Alginate/Chitosan NPs for antitumor efficacy against breast cancer. ß-Sitosterol-loaded Alginate/Chitosan nanoparticles (ß-SIT-Alg/Ch-NPs) were fabricated using an ion-gelation technique, and then the NPs' surfaces were activated using an EDC/sulfo-NHS conjugation reaction. The activated chitosan NPs werefunctionalized with folic acid (FA), leveled as ß-SIT-Alg/Ch-NPs-FA. Moreover, the functionalized NPs were characterized for size distribution, polydispersity index (PDI), and surface charge, FT-IR and DSC. ß-SIT released from ß-SIT-Alg/Ch-NPs was estimated in various biorelevant media of pH 7.4, 6.5, and 5.5, and data werefitted into various kinetic models. The cytotoxic study of ß-SIT-Alg/Ch-NPs-FA against the cancer cell line was established. The antioxidant study of developed ß-SIT-Alg/Ch-NPs was performed using DPPH assay. The stability of developed optimized formulation was assessed in phosphate buffer saline (PBS, pH 7.4), as per ICH guidelines. The drug-entrapped Alg/Ch-NPs-FA appeared uniform and nonaggregated, and the nanoscale particle measured a mean size of 126 ± 8.70 nm. The %drug encapsulation efficiency and %drug loading in ß-SIT-Alg/Ch-NPs-FA were 91.06 ± 2.6% and 6.0 ± 0.52%, respectively. The surface charge on ß-SIT-Alg/Ch-NPs-FA was measured as +25 mV. The maximum ß-SIT release from ß-SIT-Alg/Ch-NPs-FA was 71.50 ± 6.5% in pH 5.5. The cytotoxic assay expressed an extremely significant antitumor effect by ß-SIT-Alg/Ch-NPs-FA when compared to ß-SIT-suspension (p < 0.001). The antioxidant capacity of ß-SIT-Alg/Ch-NPs-FA was 91 ± 5.99% compared to 29 ± 8.02% for ß-SIT-suspension. The stability of NPs noticed an unworthy alteration (p > 0.05) in particle sizes and other parameters under study in the specific period.

Bioinspired and biomimetic micro- and nanostructures in biomedicine.

Bioinspired and biomimetic micro- and nanostructures have a high significance in the field of biomedicine. In this review, the possible applications of these micro- and nanostructures that come across in our daily life and inspired by nature itself are presented. Also, the biomimetic and bioinspired systems related to micro- and nanostructures in biomedicine are also described. The role of bioinspired and biomimetic micro- and nanostructures in therapeutics, especially in anti-inflammatory and wound healing, development of bioinspired medical devices, tissue engineering, drug delivery, gene delivery, pressure sensors, and bioprinting are discussed. The biomimetic and bioinspired systems using carbon-based nanostructures, polymer nanocomposites, hybrid scaffolds, polymer networks,and protein nanostructures are also reviewed. The advantage of these bioinspired and biomimetic structures is derived from their high biocompatibility when compared to the synthetically derived micro-/nanostructures. By developing deeper knowledge and overcoming the associated challenges, these micro- and nanostructures present a promising solution for many unresolved problems in biomedicine.

Optimized D-α-tocopherol polyethylene glycol succinate/phospholipid self-assembled mixed micelles: A promising lipid-based nanoplatform for augmenting the antifungal activity of fluconazole.

Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested in vivo for the antifungal activity against C. albicans in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis.

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics.

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of -15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 µm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson's Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.

Lung Targeted Lipopolymeric Microspheres of Dexamethasone for the Treatment of ARDS.

Acute respiratory distress syndrome (ARDS), a catastrophic illness of multifactorial etiology, involves a rapid upsurge in inflammatory cytokines that leads to hypoxemic respiratory failure. Dexamethasone, a synthetic corticosteroid, mitigates the glucocorticoid-receptor-mediated inflammation and accelerates tissue homeostasis towards disease resolution. To minimize non-target organ side effects arising from frequent and chronic use of dexamethasone, we designed biodegradable, lung-targeted microspheres with sustained release profiles. Dexamethasone-loaded lipopolymeric microspheres of PLGA (Poly Lactic-co-Glycolic Acid) and DPPC (Dipalmitoylphosphatidylcholine) stabilized with vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate) were prepared by a single emulsion technique that had a mean diameter of 8.83 ± 0.32 µm and were spherical in shape as revealed from electron microscopy imaging. Pharmacokinetic and biodistribution patterns studied in the lungs, liver, and spleen of Wistar rats showed high selectivity and targeting efficiency for the lung tissue (re 13.98). As a proof-of-concept, in vivo efficacy of the microspheres was tested in the lipopolysaccharide-induced ARDS model in rats. Inflammation markers such as IL-1ß, IL-6, and TNF-α, quantified in the bronchoalveolar lavage fluid indicated major improvement in rats treated with dexamethasone microspheres by intravenous route. Additionally, the microspheres substantially inhibited the protein infiltration, neutrophil accumulation and lipid peroxidation in the lungs of ARDS bearing rats, suggesting a reduction in oxidative stress. Histopathology showed decreased damage to the pulmonary tissue upon treatment with the dexamethasone-loaded microspheres. The multipronged formulation technology approach can thus serve as a potential treatment modality for reducing lung inflammation in ARDS. An improved therapeutic profile would help to reduce the dose, dosing frequency and, eventually, the toxicity.

Coconut oil-based resveratrol nanoemulsion: Optimization using response surface methodology, stability assessment and pharmacokinetic evaluation.

Phytochemicals are widely studied for therapeutic applications and nanostructured delivery systems for phytochemicals are under spotlight. Resveratrol is a promising candidate for neurodegenerative disorders. In the present study, we aimed to formulate nanoemulsion of resveratrol by ultrasonication process using response surface methodology. The effect of both formulation and ultrasonication process factors were studied for the nanoemulsification process using coconut oil, Pluronic-P107, and Cremophor EL. The time, intensity, and power of ultrasonication were selected as process factors. The globule size, PDI, and zeta potential were the responses selected. The concentrations of oil and surfactant and the intensity were found to significantly influence the globule size. The concentration of resveratrol in the optimized nanoemulsion formulation was 2.6442 mg/ml. The in vitro drug release in pH 6.8 phosphate buffer as well as in vitro permeation study on goat nasal mucosa proved the superiority of the nanoemulsion formulation. On intranasal administration in the rat at a resveratrol dose of 2 mg/kg, the brain targeting efficacy of the nanoemulsion formulation was high. Overall, this research provides the benefit of intake of resveratrol containing fruits and, its incorporation into nanoemulsions system could be a promising alternative for the management of Alzheimer's disease.

2-Methoxy-estradiol Loaded Alpha Lipoic Acid Nanoparticles Augment Cytotoxicity in MCF-7 Breast Cancer Cells.

The therapeutic effectiveness of anticancer drugs with a selective target for the nucleus of cancer cells may be improved by experimental approaches. In this regard, the formulation of anticancer drugs is considered one of the best ways to improve their effectiveness in targeting cancerous tissues. To enhance the anticancer activity of 2-methoxy-estradiol (2 ME) for breast cancer, 2-methoxyestradiol loaded alpha lipoic acid nanoparticles have been formulated. The prepared formula was observed to be spherical with a nanometer-scale and low PDI size (.234). The entrapment efficiency of the 2ME-ALA NPs was 87.32 ± 2.21% with > 85% release of 2 ME within 24 h. There was a 1.2-fold increase in apoptosis and a 3.46-fold increase in necrosis of the MCF-7 cells when incubated with 2ME-ALA NPs when compared to control cells. This increased apoptosis was also associated with increased ROS and increased p53 expression in 2ME-ALA NPs treated cells compared to the raw-2 ME group. Evaluation of cell-cycle data showed a substantial arrest of the G2-M phase of the MCF-7 cells when incubated with 2ME-ALA NPs. At the same time, a dramatically increased number of pre-G1 cells showed the increased apoptotic potential of the 2 ME when administered via the proposed formulation. In the end, the differential upregulation of caspase-3, p53, and ROS in MCF-7 cells established the superiority of the 2ME-ALA-Ms approach in targeting breast cancer. In summary, these results demonstrate that 2ME-ALA NPs are an efficient delivery tool for controlling the growth of breast cancer cells.

Combating the Pandemic COVID-19: Clinical Trials, Therapies and Perspectives.

The coronavirus disease-19 (COVID-19) is caused due to the infection by a unique single stranded enveloped RNA virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The COVID-19 has claimed many lives around the globe, and a promising solution to end this pandemic is still awaited. Till date neither an exact antiviral drug nor a vaccine is available in the market for public use to cure or control this pandemic. Repurposed drugs and supportive measures are the only available treatment options. This systematic review focuses on different treatment strategies based on various clinical studies. The review discusses all the current treatment plans and probable future strategies obtained as a result of a systematic search in PubMed and Science Direct database. All the possible options for the treatment as well as prophylaxis of COVID-19 are discussed. Apart from this, the article provides details on the clinical trials related to COVID-19, which are registered under ClinicalTrials.gov. Potential of drugs based on the previous researches on SARS-CoV, MERS-CoV, Ebola, influenza, etc. which fall under the same category of coronavirus are also emphasized. Information on cell-based and immunology-based approaches is also provided. In addition, miscellaneous therapeutic approaches and adjunctive therapies are discussed. The drug repurposing options, as evidenced from various in vitro and in silico models, are also covered including the possible future solutions to this pandemic.

Effect of Nardostachys jatamansi DC. on Apoptosis, Inflammation and Oxidative Stress Induced by Doxorubicin in Wistar Rats.

The study aimed to investigate the protective action of jatamansi (Nardostachys jatamansi DC.) against doxorubicin cardiotoxicity. Methanolic extract of jatamansi (MEJ) was prepared and standardized using HPTLC fingerprinting, GC-MS chemoprofiling, total phenolic content, and antioxidant activity in vitro. Further in vivo activity was evaluated using rodent model. Animals were divided into five groups (n = 6) namely control (CNT) (Normal saline), toxicant (TOX, without any treatment), MEJ at low dose (JAT1), MEJ at high dose (JAT2), and standard desferrioxamine (STD). All groups except control received doxorubicin 2.5 mg per Kg intra-peritoneally for 3 weeks in twice a week regimen. After 3 weeks, the blood samples and cardiac tissues were collected from all groups for biochemical and histopathological evaluation. Treatment with MEJ at both dose levels exhibited significant reduction (p < 0.001 vs. toxicant) of serum CK-MB (heart creatine kinase), LDH (Lactate dehydrogenase) & HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) levels, and tissue MDA (melondialdehyde) level; insignificant difference was observed (p > 0.05) in TNF-alpha (tumour necrosis factor), IL-6 (interleukine-6) levels and caspase activity as compared to TOX. Histopathological evaluation of cardiac tissues of different treatment groups further reinforced the findings of biochemical estimation. This study concludes that jatamansi can protect cardiac tissues from oxidative stress-induced cell injury and lipid peroxidation as well as against inflammatory and apoptotic effects on cardiac tissues.

Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS.

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. METHODS: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box-Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. RESULTS: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. CONCLUSION: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route.

In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain-blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood-brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus.