Pharmaceutical applications of therapeutic deep eutectic systems (THEDES) in maximising drug delivery.

The issue of poor solubility of active pharmaceutical ingredients (APIs) has been a salient area of investigation and novel drug delivery systems are being developed to improve the solubility of drugs, enhance their permeability and thereby their efficacy. Several techniques for solubilization enhancement of poorly soluble drugs are often employed at various stages of pharmaceutical drug product development. One such delivery system is the therapeutic deep eutectic system (THEDES), which showed great potential in the enhancement of solubility and permeability of drugs and ultimately augmenting their bioavailability. THEDES are made by mixing drugs with deep eutectic solvents (DESs) in a definite molar ratio by the hit and trial method. The DESs are a new class of green solvents which are non-toxic, cheap, easy to prepare, biodegradable and have multiple applications in the pharmaceutical industry. The terminologies such as ionic liquids (ILs), DES, THEDES, and therapeutic liquid eutectic systems (THELES) have been very much in use recently, and it is important to highlight the pharmaceutical applications of these unexplored reservoirs in drug solubilization enhancement, drug delivery routes, and in the management of various diseases. This review is aimed at discussing the components, formulation strategies, and routes of administration of THEDES that are used in developing the formulation. Also, the major pharmaceutical applications of THEDES in the treatment of various metabolic and non-metabolic diseases are reviewed.

Correction: Shakir et al. Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers. Pharmaceuticals 2022, 15, 686.

In the original publication, a mistake was observed in Figure 5 as published [...].

Structural, mechanical, barrier and antioxidant properties of pectin and xanthan gum edible films loaded with grapefruit essential oil.

This research focused on the development of films based on pectin and xanthan gum composite loaded with different concentrations of grapefruit essential oil (GFO). The fabricated films were characterized to assess the effect of GFO on the structural, mechanical, barrier, chemical, and antioxidant properties. The addition of GFO enhanced the functional properties of the films, as confirmed by FTIR analysis showing molecular interactions within the film matrix. SEM observations revealed that films with higher GFO content had a smoother, more compact structure with uniform oil distribution. Films loaded with oil demonstrated enhanced water resistance, as their decreased permeability ranged from 0.733 ± 0.009 to 0.561 ± 0.020 (g mm)/(m2.h.kPa). Additionally, these films showed a notable increase in tensile strength, ranging from 2.91 ± 0.19 to 8.55 ± 0.62 MPa. However, the addition of oil led to a reduction in the elongation at break of the films, which decreased from 52.84 ± 3.41 % to 12.68 ± 1.52 %, and a decline in transparency from 87.57 ± 0.65 % to 76.18 ± 1.12 %. Fabricated films exhibited enhanced antioxidant properties, as evidenced by increased DPPH• and ABTS•+ radical scavenging activities with the addition of GFO. The findings of the current study suggest that GFO is an effective natural additive for enhancing the physiochemical properties of pectin and xanthan gum-based films, making them more suitable for food packaging applications.

Evaluation of the Inhibitory Effect of Moringa oleifera Leaves Methanolic Extract against In Vitro Growth of Several Babesia Species and Theileria equi and the In Vivo Growth of Babesia microti.

The current study evaluated the inhibitory effect of Moringa oleifera leaves methanolic extract (MOL) against the in vitro growth of Babesia bovis (B. bovis), B. caballi, B. bigemina, and Theileria equi (T. equi), as well as in vivo growth of B. microti in mice. Active principles of MOL extract were determined using liquid chromatography mass spectrometry (LC-MS). MOL's anti-piroplasm efficacy was assessed both in vitro and in vivo using the SYBR Green I fluorescence assay. Every 96 hours, the hematological parameters, including red blood cell count (RBCs; 104/UL), hemoglobin content (HGB; g/dl), and hematocrit percent (HCT; %), in the treated mice were monitored using a Celltac MEK6450 automated hematological analyzer. LC-MS of MOL revealed that the most abundant polyphenolic catechism found in the MOL extract was isoquercetin and rutin. MOL inhibited B. bovis, B. caballi, B. bigemina, and T. equi in vitro growth in a dose-dependent way, with IC50 values of 45.29 ± 6.14, 19.16 ± 0.45, 137.49 ± 16.07, and 9.29 ± 0.014 µg/ml, respectively. MOL's in vitro antibabesial activity was enhanced when administrated simultaneously with either diminazene aceturate (DA) or MMV665875 compound from malaria box. In mice infected by B. microti, a combination of MOL and a low dose of DA (12.5 mg·kg-1) resulted in a significant (P < 0.05) reduction in B. microti growth. These findings suggest that MOL is an effective herbal anti-piroplasm therapy, especially when combined with a low dosage of either DA or MMV665875.

Structure-based virtual screening of natural compounds as inhibitors of HCV using molecular docking and molecular dynamics simulation studies.

The hepatitis C virus (HCV), which causes hepatitis C, is a viral infection that damages the liver and causes inflammation in the liver. New potentially effective antiviral drugs are required for its treatment owing to various issues associated with the existing medications, including moderate to severe adverse effects, higher costs, and the emergence of drug-resistant strains. The objective of the current study was to utilize computational techniques to assess the anti-HCV efficacy of certain phytochemicals against tetraspanin (CD81) and claudin 1 (CLDN1) entry proteins. A 200-nanosecond molecular dynamics (MD) simulation was employed to examine the stability of the lead-protein complexes. Free binding energy and molecular docking calculations were conducted utilizing MM/GBSA method, and the selectivity of hit compounds for CD81 and CLDN1 was determined. Five significant CD81 and CLDN1 inhibitors were identified: Petasiphenone, Silibinin, Tanshinone IIA, Taxifolin, and Topaquinone. The MM/GBSA analysis of the compounds revealed high free binding energies. All the identified compounds were stable within the CD81 and CLDN1 binding pockets. This study indicated the promising inhibitory potential of the identified compounds against CD81 and CLDN1 receptors and might develop into potential viral entry inhibitors. However, to validate the chemotherapeutic capabilities of the discovered leads extensive preclinical research is required.Communicated by Ramaswamy H. Sarma.

Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage.

The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was - 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at - 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at 2θ angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R2 value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1ß, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at p < 0.001.

Design, physicochemical characterisation, and in vitro cytotoxicity of cisplatin-loaded PEGylated chitosan injectable nano / sub-micron crystals.

The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The 1H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The 13C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm-1. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R2 value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats.

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

Production, Characterization, and In Vitro and In Vivo Studies of Nanoemulsions Containing St. John's Wort Plant Constituents and Their Potential for the Treatment of Depression.

The current project was designed to prepare an oil-in-water (oil/water) hypericin nanoemulsion using eucalyptus oil for the preparation of an oil phase with chitosan as an emulsion stabilizer. The study might be a novelty in the field of pharmaceutical sciences, especially in the area of formulation development. Tween® 80 (Polysorbate) was used as the nonionic surfactant. The nanoemulsion was prepared by using the homogenization technique, followed by its physicochemical evaluation. The surface morphological studies showed the globular structure has a nano-sized diameter, as confirmed by zeta size analysis. The zeta potential analysis confirmed a positive surface charge that might be caused by the presence of chitosan in the formulation. The pH was in the range of 5.14 to 6.11, which could also be compatible with the range of nasal pH. The viscosity of the formulations was found to be affected by the concentration of chitosan (F1-11.61 to F4-49.28). The drug release studies showed that the presence of chitosan greatly influenced the drug release, as it was noticed that formulations having an elevated concentration of chitosan release lesser amounts of the drug. The persistent stress in the mouse model caused a variety of depressive- and anxiety-like behaviors that can be counteracted by chemicals isolated from plants, such as sulforaphane and tea polyphenols. In the behavioral test and source performance test, hypericin exhibited antidepressant-like effects. The results show that the mice treated for chronic mild stress had a considerably higher preference for sucrose after receiving continuous hypericin for 4 days (p = 0.0001) compared to the animals administered with normal saline (p ≤ 0.0001) as well as the naïve group (p ≤ 0.0001). In conclusion, prepared formulations were found to be stable and can be used as a potential candidate for the treatment of depression.

Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats.

Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values.

One-pot green synthesis of gold nanoparticles using Sarcophyton crassocaule, a marine soft coral: Assessing biological potentialities of antibacterial, antioxidant, anti-diabetic and catalytic degradation of toxic organic pollutants.

Marine bio-resources are being extensively researched as a priceless supply of substances with therapeutic potential. This work report the first time attempt made towards the green synthesis of gold nanoparticles (AuNPs) using the aqueous extract of marine soft coral (SCE), Sarcophyton crassocaule. The synthesis was conducted under optimized conditions and the visual coloration of reaction mixture changed from yellowish to ruby red at 540 nm. The electron microscopic (TEM, SEM) studies exhibited spherical and oval shaped SCE-AuNPs in the size ranges of 5-50 nm. The organic compounds present in SCE were primarily responsible for the biological reduction of gold ions validated by FT-IR while the zeta potential confirmed the overall stability of SCE-AuNPs. The synthesized SCE-AuNPs exhibited variety of biological efficacies like antibacterial, antioxidant and anti-diabetic in nature. The biosynthesized SCE-AuNPs demonstrated remarkable bactericidal efficacy against clinically significant bacterial pathogens with inhibition zones of mm. Additionally, SCE-AuNPs exhibited greater antioxidant capacity in terms of DPPH: 85 ± 0.32% and RP: 82 ± 0.41%). The ability of enzyme inhibition assays to inhibit α-amylase (68 ± 0.21%) and α-glucosidase (79 ± 0.2%) was quite high. The study also highlighted the spectroscopic analysis of the biosynthesized SCE-AuNPs' catalytic effectiveness of 91% in the reduction processes of the perilous organic dyes, exhibiting pseudo-first order kinetics.

Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains.

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1ß, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker's enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Induction of Innate and Adaptive Immune Response against Recombinant HBsAg Protein Entrapped in Docosahexaenoic Acid Nanovesicles through Biomarkers.

The present study focused on demonstrating the induction of humoral and cell-mediated immunity through the establishment of a cytokine network. We hypothesized the anti-inflammatory, pro-inflammatory, and IgE antibody levels after vaccination with lyophilized recombinant HBsAg-loaded docosahexaenoic acid nanovesicles (LRPDNV), and the efficacy compared well with standard commercial recombinant hepatitis B vaccine. The cytokine network was efficiently regulated by striking a balance between pro-inflammatory cytokines IL-6, IL-8R, and IL-12 and anti-inflammatory cytokines such as IL-2, IL-4, IL-10, and IFN-γ immune response on the 14th and 30th day after primary and booster immunization. The acute phase protein CRP level was increased due to IL-6 after immunizing with LRPDNV. On the other hand, the IgE level was not significantly increased to induce any allergic reactions after immunization with LRPDNV. The study concluded that after immunizing with LRPDNV, a significant immunological response was established, implying that DHA nanovesicles have significant potential as an adjuvant method for delivering recombinant HBsAg protein. On the other hand, following immunization with LRPDNV, the IgE level was not noticeably elevated enough to cause any adverse reactions. The study concludes that a robust immune response was developed after immunizing with LRPDNV and suggests that DHA nanovesicles have much potential to deliver recombinant HBsAg protein.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Osmotic Pump Drug Delivery Systems-A Comprehensive Review.

In the last couple of years, novel drug delivery systems (NDDS) have attracted much attention in the food and pharmaceutical industries. NDDS is a broad term that encompasses many dosage forms, one of which is osmotic pumps. Osmotic pumps are considered to be the most reliable source of controlled drug delivery, both in humans and in animals. These pumps are osmotically controlled and release active agents through osmotic pressure. To a large extent, drug release from such a system is independent of gastric fluids. Based on such unique properties and advantages, osmotic pumps have made their mark on the pharmaceutical industry. This review summarizes the available osmotic devices for implantation and osmotic tablets for oral administration.

Targeting Nanotechnology and Nutraceuticals in Obesity: An Updated Approach.

HYPOTHESIS: This review article represents a brief layout of the risk factors and pathophysiology responsible for obesity, customary treatment strategies, and nanotechnology-based nutraceutical for the therapeutics of obesity. EXPERIMENTS: An exhaustive search of the literature was done for this purpose, using Google Scholar, PubMed, and ScienceDirect databases. A literature study was conducted using publications published in peer-reviewed journals between 2000 and 2022. FINDINGS: This was revealed that risk factors responsible for obesity were genetic abnormalities and environmental and socio-economic factors. Several research articles published between 2000 and 2022 were based on phytoconstituents-based nanoformulation for obesity therapeutics and, therefore, have been systematically compiled in this review. Various nutraceuticals like Garcinia cambogia, quercetin, resveratrol, capsaicin, Capsicum, Curcuma longa, Camella Sinensis, Zingiber officinalis, Citrus aurantium, Aegle marmelos, Coffea canephora, Asparagus officinalis, Gardenia jasminoides, Catha edulis, Clusia nemroisa, Rosmarinus officinalis, Cirsium setidens, Betula platyphylla, Tripterygium wilfordi possessing anti-obesity actions are discussed in this review along with their patents, clinical trials as well as their nanoformulation available. CONCLUSION: This review illustrates that nanotechnology has a great propensity to impart a promising role in delivering phytochemicals and nutraceuticals in managing obesity conditions and other related disorders.

Fast dissolving oral films: An approach to co-load and deliver the atorvastatin and ezetimibe for better therapeutic response.

Atherosclerotic patients suffering with acute coronary disease are lying at high risk. This life-threatening problem can be curtailed by using statins e.g., ezetimibe (EZT), atorvastatin calcium (ATC). In this study, co-loaded Fast Dissolving oral films (FDOFs), of ATC-EZT with HPMC E5 prepared by solvent evaporation method. Prepared FDOFs were evaluated for physicochemical, thermal and mechanical properties. In-vivo animal studies were performed on albino rats against diet induced hyperlipidemia. Prepared FDOFs have rapid DT; 27sec, TDT >2min and in-vitro drug release 97% in a min. In DSC, FTIR and XRD analysis, prepared films were chemically compatible and no chemical interaction of drugs and excipient was found. In kinetic modeling, it was observed their EZT exhibited lowest R2 value for zero order kinetic and best fit model was first order kinetic (n, 0.9823). The korsmeyer peppas model films (n, 0.016) indicate fickian type drug diffusion. The groups treated with marketed suspension of drug and FODPs were compared with normal group and high fats diet group. Study reviled that combination FDOPs of both ATC/EZT significantly reduce hyperlipemia as compared to high fat diet group. It can be concluded that ATC and EZT encapsulated in FODFs provide instant drug release and better therapeutic outcomes.

State-of-the-art Tools to Elucidate the Therapeutic Potential of TAT-peptide (TP) Conjugated Repurposing Drug Against SARS-CoV-2 Spike Glycoproteins.

BACKGROUND: In late 2019, a highly infectious and pathogenic coronavirus was recognized as Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), which causes acute respiratory disease, threatening human health and public safety. A total of 448,327,303 documented cases and 6,028,576 deaths have been reported as of March 8th 2022. The COVID-19 vaccines currently undergoing clinical trials or already in use should provide at least some protection against SARS-CoV-2; however, the emergence of new variations as a result of mutations may lessen the effectiveness of the currently available vaccines. Since the efficacy of available drugs and vaccines against COVID-19 is notably lower, there is an urgent need to develop a potential drug to treat this deadly disease. The SARS-CoV-2 spike (SCoV-SG) is the foremost drug target among coronaviruses. OBJECTIVE: The major objectives of the current study are to conduct a molecular docking study investigation of TAT-peptide47-57(GRKKRRQRRRP)-conjugated remodified therapeutics such as ritonavir (RTV), lopinavir (LPV), favipiravir (FPV), remdesivir (RMV), hydroxychloroquine (HCQ), molnupiravir (MNV) and nirmatrelvir (NMV) with (SCoV-SG) structure. METHODS: Molecular docking analysis was performed to study the interaction of repurposed drugs and drugs conjugated with the TAT-peptide with target SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) using Auto- Dock. Further docking investigation was completed with PatchDock and was visualized by the discovery of the studio visualizer 2020. RESULTS: TAT-peptides are well-characterized immune enhancers that are used in intracellular drug delivery. The results of molecular docking analysis showed higher efficiency and significantly enhanced and improved interactions between TP-conjugated repurposed drugs and the target sites of the SCoV-SG structure. CONCLUSION: The study concluded that TP-conjugated repurposed drugs may be effective in preventing COVID- 19, and therefore, in vitro, in vivo, and clinical trial studies are required in detail.

Insights into the pivotal role of statins and its nanoformulations in hyperlipidemia.

Hyperlipidemia is the primary cause of heart disorders and has been manifested as the condition with remarkable higher levels of very-low-density lipoproteins, low-density lipoproteins, intermediate-density lipoprotein, triglycerides, and cholesterol in blood circulation. Genetic causes or systemic metabolic illnesses like diabetes mellitus, increased alcohol consumption, hypothyroidism, and primary biliary cirrhosis are several reasons behind development of hyperlipidemia. Higher levels of lipids and lipoproteins in plasma are responsible for various health disorders in human body like occlusion of blood vessels, acute pancreatitis, and reduced artery lumen elasticity. Both primary and secondary prophylaxis of heart disease can be achieved through combination of pharmacologic therapy with therapeutic lifestyle adjustments. Statins which belongs to HMG-CoA reductase inhibitors are preferred for primary prevention of hyperlipidemia particularly for individuals at higher risk of development of heart disease. This review discusses the recent advancements and outcomes of nanoparticle drug carriers for statins in the therapy of hyperlipidemia.

Biofabrication of Silver Nanoparticles (AgNPs) Using Embelin for Effective Therapeutic Management of Lung Cancer.

Nanobiotechnology is a burgeoning field of research with applications in cancer treatment, targeted chemotherapy, and molecular diagnosis. This study aims at the fabrication of silver nanoparticles using embelin derived from Embelia ribes to evaluate its anticancer property. Silver nanoparticles (AgNPs) have emerged as a novel nano-carrier for therapeutic agents with a wide range of medical capabilities due to their unique structural, physicochemical, and optical features. In our study, the particle size of fabricated AgNPs was measured as 25 nm, and the zeta potential was recorded as -5.42 mV, which indicates the good stability of embelin-derived AgNPs. The crystalline surface morphology was observed by SEM analysis. The FT-IR spectrum confirmed the reduction in silver ions (Ag+) by embelin, and the TEM analysis exhibited polydispersed Ag+ of 20-30 nm. The anticancer potential of embelin-fabricated AgNPs was investigated using in vitro studies on lung cancer cells by the MTT assay. The results revealed significant dose-dependent inhibition of cell proliferation against A549 cell lines. Embelin AgNP-induced apoptosis was measured by the annexin-V PI apoptosis assay, which exhibited significantly low necrotic cells as compared to apoptotic cells. Finally, the findings of our study suggest the anticancer potential of biofabricated embelin AgNPs, particularly against lung cancer cells.