Tamarindus indica L., is widely used tree in ayurvedic medicine. Here, we aimed to understand the presence of important constituents in seeds and peel of Tamarind fruits and their biological activities. Hence, seeds and peel of Tamarind fruits are used for further extraction process by soxhlet method (chloroform and ethyl acetate solvents). Results suggest that the ethyl acetate extract (seeds) consists of terpenoids (72.29 ± 0.513 mg/g), phenolic content (68.67 ± 2.11 mg/g) and flavonoids (26.36 ± 2.03 mg/g) whereas chloroform extract (seeds) has terpenoids (42.29 ± 0.98 mg/g). Similarly, chloroform extract (peel) has terpenoids (25.96 ± 3.20 mg/g) and flavonoids (46.36 ± 2.03 mg/g) whereas ethyl acetate extract (peel) has terpenoids (62.93 ± 0.987 mg/g). Furthermore, anti-inflammation activity results revealed that the chloroform extract of peel was found to be more effective with IC50 of 226.14 µg/ml by protein denaturation analysis and with IC50 of 245.5 µg/ml on lipoxygenase inhibition activity. Chloroform extract (peel and seeds) shown better antioxidant activity using DPPH than ethyl acetate extract (peel and seeds). Ethyl acetate extract of seeds showed impressive potency by inhibiting the growth of fungus, Candida albicans. Additionally, ethyl acetate extract of seeds showed impressive potency inhibiting the growth of Escherichia coli than Bacillus cereus. GC-MS analysis shown the existence of diverse set of phytochemicals in each extract. Overall, comparative studies highlight the effectiveness of seeds extracts than peel extracts. Moreover, GC-MS results suggest that the seeds and peel extracts (chloroform and ethyl acetate) contains a wide range of compounds (including flavonoids, isovanillic acid, fatty acids and phenolic compounds) which can be utilized for therapeutic purpose.
The primary objective of the research effort is to establish efficient solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for benidipine (BD) through the systematic application of a quality-by-design (QbD)-based paradigm. Utilizing Labrafil M 2125 CS, Kolliphor EL, and Transcutol P, the BD-S-SNEDDS were created. The central composite design was adopted to optimize numerous components. Zeta potential, drug concentration, resistance to dilution, pH, refractive index, viscosity, thermodynamic stability, and cloud point were further investigated in the most efficient formulation, BD14, which had a globule size of 156.20 ± 2.40 nm, PDI of 0.25, zeta potential of -17.36 ± 0.18 mV, self-emulsification time of 65.21 ± 1.95 s, % transmittance of 99.80 ± 0.70%, and drug release of 92.65 ± 1.70% at 15 min. S-SNEDDS were formulated using the adsorption process and investigated via Fourier transform infrared spectroscopy, Differential scanning calorimeter, Scanning electron microscopy, and powder X-ray diffraction. Optimized S-SNEDDS batch BD14 dramatically decreased blood pressure in rats in contrast to the pure drug and the commercial product, according to a pharmacodynamics investigation. Accelerated stability tests validated the product's stability. Therefore, the development of oral S-SNEDDS of BD may be advantageous for raising BD's water solubility and expanding their releasing capabilities, thereby boosting oral absorption.
Biological Products , Nanoparticles , Rats , Animals , Nanoparticle Drug Delivery System , Emulsions/chemistry , Biological Availability , Drug Delivery Systems/methods , Solubility , Drug Liberation , Particle Size , Administration, Oral , Nanoparticles/chemistry , Surface-Active Agents/chemistry
Nisoldipine (NIS) is a calcium channel blocker that exhibits poor bioavailability (~5%) due to low aqueous solubility and presystemic metabolism in the gut wall. In this context, the present work aimed to develop NIS solid dispersion (NISSD)-based sublingual films using solvent casting technique to improve the dissolution. Phase solubility studies indicated that Soluplus® was the most effective carrier for improving the aqueous solubility of NIS. NISSDs were initially developed using the solvent evaporation method. Fourier transform infrared spectrometric studies were found to display the characteristic vibrational bands related to C=O stretching and N-H deformation in NISSDs, proving the chemical integrity of the drug in NISSDs. Subsequently, bioadhesive sublingual films of NISSDs were formulated using solvent casting method, using hydroxypropyl methyl cellulose (HPMC) E5, E15, and hydroxy ethyl cellulose (HEC EF) as hydrophilic polymers and polyethylene glycol 400 (PEG 400) as plasticizer. The incorporation of NISSDs was found to produce clear films that displayed uniform content. The sublingual film of NISSDs composed of HPMC E5 (2% w/v), was found to display the least thickness (0.29 ± 0.02 mm), the highest folding endurance (168.66 ± 4.50 times), and good bioadhesion strength (12.73 ± 0.503 g/cm2). This film was found to rapidly disintegrate (28.66 ± 3.05 sec) and display near-complete drug release (94.24 ± 1.22) in 30 min. Incorporating NISSDs into rapidly bioadhesive sublingual films considerably improves drug dissolution. Overall, these research outcomes underscored the potential of rapidly dissolving bioadhesive sublingual films to evade gut metabolism and resolve the bioavailability issues associated with oral administration of NIS.
Nanoneedles (NN) are growing rapidly as a means of navigating biological membranes and delivering therapeutics intracellularly. Nanoneedle arrays (NNA) are among the most potential resources to achieve therapeutic effects by administration of drugs through the skin. Although this is based on well-established approaches, its implementations are rapidly developing as an important pharmaceutical and biological research phenomenon. This study intends to provide a broad overview of current NNA research, with an emphasis on existing approaches, applications, and types of compounds released by these systems. A nanoneedle-based delivery device with great spatial and temporal accuracy, minimal interference, and low toxicity could transfer biomolecules into living organisms. Due to its vast potential, NN has been widely used as a capable transportation system of many therapeutic active substances, from cancer therapy, vaccine delivery, cosmetics, and bio-sensing nanocarrier drugs to genes. The use of nanoneedles for drug delivery offers new opportunities for the rapid, targeted, and exact administration of biomolecules into cell membranes for high-resolution research of biological systems, and it can treat a wide range of biological challenges. As a result, the literature has analyzed existing patents to emphasize the status of NNA in biological applications.
Drug Delivery Systems , Skin , Cell Membrane
Polyherbal formulation (PHF) enhances therapeutic efficacy and minimizes side effects by reducing individual herb dosages. Allopolyherbal formulation (APHF) combines polyherbal extracts with allopathic medication, effectively reducing the latter's required dose and mitigating associated adverse effects. The current study intends to assess the anti-diabetic effects of PHF and APHF in-vivo. Dried raw powders of Cassia auriculata leaf, Centella asiatica leaf, and Zingiber officinale rhizome were extracted by cold maceration process using 70% ethanol. These extracts were combined in three different ratios to make PHF. PHF was subjected to qualitative and quantitative phytochemical investigations. APHF has been prepared by combining a potent ratio of PHF with metformin in three different ratios. The compatibility of APHF has been confirmed by differential scanning calorimetry (DSC). In vivo activity was also evaluated in streptozotocin-induced diabetic albino rats. PHF (3 different ratios at a dose of 200-400 mg/kg b.w), APHF (combination of PHF and metformin in 3 different ratios, 200 + 22.5, 200 + 45, and 200 + 67.5 mg/kg b.w), and metformin (90 mg/kg b.w) were administered to albino rats for 21 consecutive days. Blood glucose levels were estimated on the 1st, 7th, 14th, and 21st days of treatment. On the 21st day, blood was collected by cardiac puncture for biochemical analysis. The liver and pancreas were isolated and subjected to histopathological analysis. PHF and APHF showed significant anti-diabetic and antihyperlipidemic efficacy. In comparison to PHF, APHF had the most promising action. The current study demonstrated that PHF and APHF are safe and efficacious drugs in the treatment of diabetes mellitus as they help to replace or lower the dose of metformin, thereby decreasing the risks of metformin.
Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.
The expression of inflammatory markers and vascular endothelial growth factor (VEGF) was found to be upregulated in various posterior ocular disorders, including diabetic retinopathy (DR). Effective delivery of therapeutic agents to the retina poses a significant challenge in ophthalmic drug delivery due to biological ocular barriers. Triamcinolone acetonide (TA) was selected as the model corticosteroid drug targeting cytokines and VEGF in DR. However, despite TA's low molecular weight and hydrophobicity, which enable it to bypass the conjunctival epithelial barrier, it doesn't efficiently exert its effect at the target site. Nanocarriers have emerged as a solution to enhance drug delivery to the retina and improve bioavailability. This study aimed to compare the effects of Triamcinolone-loaded cubic liquid crystalline nanoparticles (TA-cubic LCNPs) and TA-Suspension in an experimental DR model administered via the subconjunctival (SCJ) route. The results demonstrated that TA-cubic LCNPs enhanced TA periocular delivery efficacy by reducing inflammatory and VEGF markers through the advanced glycation end products (AGE)/protein kinase C pathway. They were identified as promising nano-carriers, exhibiting potential for targeted delivery to the retina.
Pioglitazone, a PPAR-gamma activator used to diagnose hyperglycemia, was studied for its stereoselective deposition and active enantiomers in female albino Wistar rats. In accordance with USFDA recommendations, a bioanalytical technique was employed to assess the segregation of pioglitazone enantiomers in rat plasma with glimepiride as an internal standard. A Phenomenox i-Amylose-3 column (150 mm × 4.6 mm) of 5 µm was used for high-performance liquid chromatography (HPLC) with a mobile phase of 10 mM ammonium acetate buffer in Millipore water and acetonitrile in 60:40 (v/v) admixture with column temperature 35 °C, wavelength 265 nm, and flow rate 0.6 mL/min, respectively. Pioglitazone-S, Pioglitazone-R, and the internal standard had retention times of 3.1, 7.4, and 1.7 min, respectively. The study found that within-run and between-run precision ranged from 0.1606-0.9889% for Pioglitazone-R and from 0.2080-0.7919% for Pioglitazone-S, while the accuracy ranged from 99.86 to 100.36% for Pioglitazone-R and 99.84 to 99.94% for Pioglitazone-S. In addition, a non-radioactive glucose uptake assay was employed to examine the enantiomers in 3T3-L1 cell lines by flow cytometry. Significant differences were demonstrated in Cmax, AUClast (h*µg/mL), AUCINF obs (h*µg/mL), and AUC%Extrap obs (%) of Pioglitazone-R and S in female albino Wistar rats, suggesting enantioselectivity of pioglitazone.
Glucose , Rats , Female , Animals , Pioglitazone , Reproducibility of Results , Rats, Wistar , Chromatography, High Pressure Liquid/methods , Stereoisomerism
A novel approach to the treatment of sinusitis is the use of nasal stents. The stent is loaded with a corticosteroid, which prevents complications in the wound-healing process. The design is such that it will prevent the sinus from closing again. The stent is 3D printed using a fused deposition modeling printer, which enhances the customization. The polymer utilized for the purpose of 3D printing is polylactic acid (PLA). The compatibility between the drugs and polymers is confirmed by FT-IR and DSC. The drug is loaded onto the polymer by soaking the stent in the drug's solvent, known as the solvent casting method. Using this method, approximately 68% of drug loading is found to be achieved onto the PLA filaments, and a total of 72.8% of drug loading is obtained in terms of the 3D-printed stent. Drug loading is confirmed by the morphological characteristics of the stent by SEM, where the loaded drug is clearly visible as white specks on the surface of the stent. Drug release characterization is conducted by dissolution studies, which also confirm drug loading. The dissolution studies show that the release of drugs from the stent is constant and not erratic. Biodegradation studies were conducted after increasing the rate of degradation of PLA by soaking it in PBS for a predetermined duration of time. The mechanical properties of the stent, such as stress factor and maximum displacement, are discussed. The stent has a hairpin-like mechanism for opening inside the nasal cavity.
Traditional eye drops used for topically administering drugs have poor ocular bioavailability due to the biological barriers of the eye. There is an interest to design and develop novel drug delivery systems that would extend the precorneal residence time, reduce the frequency of administration and decrease dose-related toxicity. This study aimed to prepare Nanoparticles of Gemifloxacin Mesylate and incorporate them into an in situ gel. The nanoparticles were prepared by ionic gelation technique, using 32 factorial design. Sodium tripolyphosphate (STPP) was used to crosslink Chitosan. The optimized formulation of the nanoparticles (GF4) contained 0.15% Gemifloxacin Mesylate, 0.15% Chitosan and 0.20% STPP, producing 71 nm particle size and 81.11% entrapment efficiency. The prepared nanoparticles showed biphasic release, with an initial burst release of 15% in 1.0 hr and a cumulative drug release of 90.53% at the end of 24 hrs. After that, the prepared nanoparticles were incorporated into an in situ gel, using Poloxamer 407, producing a sustained drug release with efficient antimicrobial activity against gram-positive and gram-negative bacteria as confirmed by the cup plate method.
Chitosan , Nanoparticles , Anti-Bacterial Agents , Gemifloxacin , Gram-Negative Bacteria , Gram-Positive Bacteria , Ophthalmic Solutions
The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold.
Immunotherapy, along with chemotherapy, targeted delivery, radiation and surgery has become one of the most common cancer treatments. The aim of cancer immunology is to use the bodys immune system to combat tumors and develop a robust antitumor immune response. In the last few years, immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have made substantial advancements in cancer immunotherapy. By boosting cell type-specific delivery and immunological responses, nanocarriers like liposomes have the ability to enhance greater immune responses. The efficacy of anti-tumor therapeutics is being significantly improved as liposomes can assist in resolving a number of issues that can arise from a variety of cancer immunotherapies. Since, liposomes can be loaded with both hydrophilic and hydrophobic drugs and protect the immunotherapeutic agents loaded inside the core, they offer significant advantages over other nano delivery systems. The use of liposomes for accurate and timely delivery of immunotherapies to particular targeted neoplasms, with little or no injury to healthy cells, maximizes immunotherapy efficacy. Liposomes are also suitable vehicles for delivering medications simultaneously with other therapies such as chemotherapy, radiation, and phototherapy. Liposomal nanoparticles will be introduced and used as an objective immunotherapy delivery system for great precision, making them a viable cancer treatment approach.With an emphasis on dendritic cells, T cells, tumor and natural killer cells, and macrophages; outline of many forms of immune-therapies in oncology and cutting-edge advances in liposomal nanovesicles for cancer immunotherapy are covered in this review.
The goal of current research was to develop a new form of effective drug, curcumin-loaded solid lipid nanoparticles (Cur-SLNs) and test its efficacy in the treatment of lung cancer. Different batches of SLNs were prepared by the emulsification-ultrasonication method. For the optimization of formulation, each batch was evaluated for particle size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). The formulation components and process parameters largely affected the quality of SLNs. The SLNs obtained with particle size, 114.9 ± 1.36 nm; PI, 0.112 ± 0.005; ZP, -32.3 ± 0.30 mV; EE, 69.74 ± 2.03%, and DL, 0.81 ± 0.04% was designated as an optimized formulation. The formulation was freeze-dried to remove excess water to improve the physical stability. Freeze-dried Cur-SLNs showed 99.32% of drug release and demonstrated a burst effect trailed by sustained release up to 120 h periods. The erythrocyte toxicity study of Cur-SLNs and its components demonstrated moderate hemolytic potential towards red blood cells (RBCs). The cytotoxic potential of the formulation and plain curcumin was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against A549 cell line. After 48 h of incubation, Cur-SLNs demonstrated more cytotoxicity (IC50 = 26.12 ± 1.24 µM) than plain curcumin (IC50 = 35.12 ± 2.33 µM). Moreover, the cellular uptake of curcumin was found to be significantly higher from Cur-SLNs (682.08 ± 6.33 ng/µg) compared to plain curcumin (162.4 ± 4.2 ng/µg). Additionally, the optimized formulation was found to be stable over the period of 90 days of storage. Hence, curcumin-loaded SLNs can be prepared using the proposed cost effective method, and can be utilized as an effective drug delivery system for the treatment of lung cancer, provided in vivo studies warrant a similar outcome.
Luliconazole is a broad-spectrum topical antifungal agent that acts by altering the synthesis of fungi cell membranes. Literature suggests that the recurrence of fungal infection can be avoided by altering the pH of the site of infection. Studies have also suggested that fungi thrive by altering skin pH to be slightly acidic, i.e., pH 3-5. The current study is aimed to design, develop, characterize, and evaluate an alkaline pH-based antifungal spray solution for antifungal effects. Luliconazole was used as an antifungal agent and an alkaline spray was formulated for topical application by using Eudragit RS 100, propylene glycol (PG), water, sodium bicarbonate, and ethanol via solubilization method. Herein, sodium bicarbonate was used as an alkalizing agent. Based on DSC, FTIR, PXRD, scanning electron microscopy (SEM), and rheological analysis outcomes, the drug (luliconazole) and polymer were found to be compatible. F-14 formulation containing 22% Eudragit RS 100 (ERS), 1.5% PG, and 0.25% sodium bicarbonate was optimized by adopting the quality by design approach by using design of experiment software. The viscosity, pH, drying time, volume of solution post spraying, and spray angle were, 14.99 ± 0.21 cp, 8 pH, 60 s, 0.25 mL ± 0.05 mL, and 80 ± 2, respectively. In vitro drug diffusion studies and in vitro antifungal trials against Candida albicans revealed 98.0 ± 0.2% drug diffusion with a zone of inhibition of 9 ± 0.12 mm. The findings of the optimized luliconazole topical film-forming solution were satisfactory, it was compatible with human skin, and depicted sustained drug release that suggests promising applicability in facilitated topical antifungal treatments.
The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of the skin. Aloe barbadensis pulp was collected and mixed with the extract of Vigna radiata and formulated into a gel using Carbopol 940, triethanolamine, and propylene glycol as the gelling agent, viscosity modifier, and pH modifier, respectively. The gel was evaluated for its antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans. Antimicrobial agents, such as gentamycin and fluconazole, were used as the standards. The developed formulation showed promising zone of inhibition. The gel was further evaluated for its physicochemical properties. The formulation showed a promising effect on acne together with the additive effect of Aloe barbadensis on skin.
Aggregation of Amyloid-ß (Aß) leads to the formation and deposition of neurofibrillary tangles and plaques which is the main pathological hallmark of Alzheimer's disease (AD). The bioavailability of the drugs and their capability to cross the BBB plays a crucial role in the therapeutics of AD. The present study evaluates the Memantine Hydrochloride (MeHCl) and Tramiprosate (TMPS) loaded solid lipid nanoparticles (SLNs) for the clearance of Aß on SHSY5Y cells in rat hippocampus. Molecular docking and in vitro Aß fibrillation were used to ensure the binding of drugs to Aß. The in vitro cell viability study showed that the M + T SLNs showed enhanced neuroprotection against SHSY5Y cells than the pure drugs (M + T PD) in presence of Aß (80.35µM ± 0.455 µM) at a 3:1 molar ratio. The Box-Behnken Design (BBD) was employed to optimize the SLNs and the optimized M + T SLNs were further characterized by %drug entrapment efficiency (99.24 ± 3.24 of MeHCl and 89.99 ± 0.95 of TMPS), particle size (159.9 ± 0.569 nm), PDI (0.149 ± 0.08), Zeta potential (-6.4 ± 0.948 mV), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and in vitro drug release. The TEM & AFM analysis showed irregularly spherical morphology. In vitro release of SLNs was noted up to 48 h; whereas the pure drugs released completely within 3 hrs. M + T SLNs revealed an improved pharmacokinetic profile and a 4-fold increase in drug concentration in the brain when compared to the pure drug. Behavioral tests showed enhanced spatial memory and histological studies confirmed reduced Aß plaques in rat hippocampus. Furthermore, the levels of Aß decreased in AlCl3-induced AD. Thus, all these noted results established that the M + T SLNs provide enhanced neuroprotective effects when compared to pure and individual drugs and can be a promising therapeutic strategy for the management of AD.
The objectives of this study were to optimize and quantify the maximum percentage yield of eupalitin-3-O-ß-D-galactopyranosidefrom Boerhavia diffusa leaves using response surface methodology (RSM), as well as to demonstrate the hepatoprotective benefits of the bioactive compound. The Box-Behnken experimental design was utilized to optimize the eupalitin-3-O-ß-D-galactopyranoside extraction procedure, which also looked at the extraction duration, temperature, and solvent concentration as independent variables. Boerhaviadiffusa leaves were extracted, and n-hexane, chloroform, ethyl acetate, and water were used to fractionate the dried extracts. The dried ethyl acetate fraction was thoroughly mixed in hot methanol and stored overnight in the refrigerator. The cold methanol was filtered, the solid was separated, and hot methanol was used many times to re-crystallize the solid to obtain pure eupalitin-3-O-ß-D-galactopyranoside (0.1578% w/w). The proposed HPTLC method for the validation and quantification of eupalitin-3-O-ß-D-galactopyranosidewassuccessfully validated and developed. The linearity (R2 = 0.994), detection limit (30 ng), and quantification limit (100 ng) of the method, as well as its range (100-5000 ng), inter and intraday precision (0.67% and 0.991% RSD), specificity, and accuracy (99.78% RSD), were all validated as satisfactory. The separation of the eupalitin-3-O-ß-D-galactopyranoside band was achieved on an HPTLC plate using toluene:acetone:water (5:15:1 v/v) as a developing system. The Box-Behnken statistical design was used to determine the best optimization method, which was found to be extraction time (90 min), temperature (45 °C), and solvent ratio (80% methanol in water v/v) for eupalitin-3-O-ß-D-galactopyranoside. Standard silymarin ranged from 80.2% at 100 µg/mL to 86.94% at 500 µg/mL in terms of significant high hepatoprotection (cell induced with carbon tetrachloride 0.1%), whereas isolated eupalitin-3-O-ß-D-galactopyranoside ranged from 62.62% at 500 µg/mL to 70.23% at 1000 µg/mL. More recently, it is a source of structurally unique flavonoid compounds that may offer opportunities for developing novel semi-synthetic molecules.
Nyctaginaceae , Silymarin , Acetates , Acetone , Carbon Tetrachloride , Chloroform , Flavonoids , Galactose , Methanol , Plant Extracts/pharmacology , Solvents , Toluene , Water
Cancer is one of the leading causes of morbidity and mortality around the globe and is likely to become the major cause of global death in the coming years. As per World Health Organization (WHO) report, every year there are over 10 and 9 million new cases and deaths from this disease. Chemotherapy, radiotherapy, and surgery are the three basic approaches to treating cancer. These approaches are aiming at eradicating all cancer cells with minimum off-target effects on other cell types. Most drugs have serious adverse effects due to the lack of target selectivity. On the other hand, resistance to already available drugs has emerged as a major obstacle in cancer chemotherapy, allowing cancer to proliferate irrespective of the chemotherapeutic agent. Consequently, it leads to multidrug resistance (MDR), a growing concern in the scientific community. To overcome this problem, in recent years, nanotechnology-based drug therapies have been explored and have shown great promise in overcoming resistance, with most nano-based drugs being explored at the clinical level. Through this review, we try to explain various mechanisms involved in multidrug resistance in cancer and the role nanotechnology has played in overcoming or reversing this resistance.
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Nanotechnology , Neoplasms/drug therapy , Neoplasms/metabolism
Cancer has long been regarded as one of the world's most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.
Neratinib (NTB) is an irreversible inhibitor of pan-human epidermal growth factor receptor (HER-2) tyrosine kinase and is used in the treatment of breast cancer. It is a poorly aqueous soluble drug and exhibits extremely low oral bioavailability at higher pH, leading to a diminishing of the therapeutic effects in the GIT. The main objective of the research was to formulate an oral raft-forming in situ gelling system of NTB to improve gastric retention and drug release in a controlled manner and remain floating in the stomach for a prolonged time. In this study, NTB solubility was enhanced by polyethylene glycol (PEG)-based solid dispersions (SDs), and an in situ gelling system was developed and optimized by a two-factor at three-level (32) factorial design. It was analyzed to study the impact of two independent variables viz sodium alginate [A] and HPMC K4M [B] on the responses, such as floating lag time, percentage (%) water uptake at 2 h, and % drug release at 6 h and 12 h. Among various SDs prepared using PEG 6000, formulation 1:3 showed the highest drug solubility. FT-IR spectra revealed no interactions between the drug and the polymer. The percentage of drug content in NTB SDs ranged from 96.22 ± 1.67% to 97.70 ± 1.89%. The developed in situ gel formulations exhibited a pH value of approximately 7. An in vitro gelation study of the in situ gel formulation showed immediate gelation and was retained for a longer period. From the obtained results of 32 factorial designs, it was observed that all the selected factors had a significant effect on the chosen response, supporting the precision of design employed for optimization. Thus, the developed oral raft-forming in situ gelling system of NTB can be a promising and alternate approach to enhance retention in the stomach and to attain sustained release of drug by floating, thereby augmenting the therapeutic efficacy of NTB.
