Antiobesity Drug Discovery Research: in vitro Models for Shortening the Drug Discovery Pipeline.

Obesity is a growing global health problem, leading to various chronic diseases. Despite standard treatment options, the prevalence of obesity continues to rise, emphasizing the need for new drugs. in vitro methods of drug discovery research provide a time and cost-saving platform to identify new antiobesity drugs. The review covers various aspects of obesity and drug discovery research using in vitro models. Besides discussing causes, diagnosis, prevention, and treatment, the review focuses on the advantages and limitations of in vitro studies and exhaustively covers models based on enzymes and cell lines from different animal species and humans. In contrast to conventional in vivo animal investigations, in vitro preclinical tests using enzyme- and cell line-based assays provide several advantages in development of antiobesity drugs. These methods are quick, affordable, and provide high-throughput screening. They can also yield insightful information about drug-target interactions, modes of action, and toxicity profiles. By shedding light on the factors that lead to obesity, in vitro tests can also present a chance for personalized therapy. Technology will continue to evolve, leading to the creation of more precise and trustworthy in vitro assays, which will become more and more crucial in the search for novel antiobesity medications.

Small Angle Neutron Scattering in Drug Discovery Research: A Novel Tool for Advanced Study of Structures of Biological Macromolecules.

Small Angle Neutron Scattering (SANS) is a powerful and novel tool for the study of soft condensed matter, including the microscopic and nanomaterials used for drug discovery and delivery. The sample is exposed to a neutron beam, and neutron scattering occurs, which is studied as a function of the scattering angle to deduce a variety of information about the dynamics and structure of the material. The technique is becoming very popular in biomedical research to investigate the various aspects of structural biology. The low-resolution information on large heterogeneous, solubilized biomacromolecular complexes in solution is obtained with the use of deuterium labelling and solvent contrast variation. The article reviews the basics of the SANS technique, its applications in drug delivery research, and its current status in biomedical research. The article covers and overviews the precise characterization of biological structures (membranes, vesicles, proteins in solution), mesoporous structures, colloids, and surfactants, as well as cyclodextrin complexes, lipid complexes, polymeric nanoparticles, etc., with the help of neutron scattering. SANS is continuously evolving as a medium for exploring the complex world of biomolecules, providing information regarding the structure, composition, and arrangement of various constituents. With improving modelling software automation in data reduction and the development of new neutron research facilities, SANS can be expected to remain mainstream for biomedical research.

Effect of Geographical Location and Type of Extract on Total Phenol/Flavon Contents and Antioxidant Activity of Different Fruits Extracts of Withania somnifera.

BACKGROUND: Withania somnifera (family solanaceae) is a well-investigated medicinal plant which is also called Indian ginseng due to its wide spectrum of medicinal properties. The contents and activity of the plant may vary depending on the habitat and part of the plant and the solvent used for extraction. The present study deals with the comparative chemical analysis and in vitro antioxidant activity of methanolic fruits extracts and its subfractions (in ethyl acetate, butanol and water) of W. somnifera collected from two different geographical locations. METHODS: In the present study, Withania somnifera fruits were collected from two different geographical locations (Uttarakhand and Rajasthan). The different fruit extracts were prepared and studied for total phenolic contents and total flavone contents. The in vitro antioxidant activity was assessed by DPPH free radical scavenging assay and peroxide scavenging assay. RESULTS: Methanol extract of W. somnifera Uttarakhand and ethyl acetate subfraction of W. somnifera Rajasthan showed the highest amount of Total Phenolic Contents (TPC). In W. somnifera Uttarakhand, ethyl acetate extract showed the highest amount of Total flavonoids while in W. somnifera Rajasthan, methanol extract was found to be the richest in flavonoids. Methanolic extract of W. somnifera Uttarakhand showed the highest free radical scavenging activity while in W. somnifera Rajasthan, the highest antioxidant activity was shown by the methanolic extract followed by butanolic extract, water extract and then ethyl acetate. In the peroxide scavenging assay of antioxidant activity, water extract of W. somnifera Uttarakhand showed the highest activity, while in W. somnifera Rajasthan, ethyl acetate extract showed highest scavenging activity. CONCLUSION: It was concluded that the geographical location exerts a vital effect on the presence of active constituents and also on the antioxidant potential of W. somnifera.

Cyclodextrin inclusion complex of racecadotril: effect of drug-ß- cyclodextrin ratio and the method of complexation.

Racecadotril is an antisecretory and antidiarrheal agent against watery diarrhoea in children. Racecadotril is a class II drug (as per Biopharmaceutical Classification System) with poor aqueous solubility and dissolution rate limited absorption. ß-cyclodextrin complexation of solubility or dissolution rate limited drugs provides an amphiphilic complex with improved solubility and dissolution profile. Thus Racecadotril - ß-cyclodextrin complex were prepared to improve its solubility and dissolution by imparting an environment of improved hydrophilicity. Racecadotril was complexed with ß-cyclodextrin (in 1:1 and 1:2 molar ratios) by two different methods (solvent evaporation and kneading method). These inclusion complexes were evaluated for solubility, drug content, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X ray powder diffraction (XRPD) and in vitro dissolution study. The highest drug content (30.83%) was found in complex made by kneading method (RK1:1) in 1:1 molar ratio. Complex prepared by solvent evaporation method (RSE1:1, RSE1:2) were found to be showing irregular disc shaped non-porous surface, while the complexes prepared by kneading method (RK1:1, RK1:2) showed rough, fluffy, non-porous and irregular surface in SEM. Solubility of the drug improved up to 2 to 3 folds in the complexes. The complex RK1:1 showed the greatest improvement in solubility (from 28.98 to76.56 µg/ml). The dissolution of the complexes was also found to be improved. Complex prepared by solvent evaporation method in 1:1 molar ratio (RSE1:1) showed a marked improvement in percent drug release (100.33%) than that of pure drug (52.58%) at the end of 1 hour in dissolution study. FTIR, DSC and XRPD data confirmed the formation of inclusion complex. It was concluded that water solubility of all the complexes were increased when the drug was complexed with ß-CD in 1:1 molar ratio. The complex made in 1:1 molar ratio (irrespective of the method) showed better solubility and the dissolution profile as compared to the complex made in 1:2 molar ratio. It was concluded that the complex prepared by the solvent evaporation method showed better solubility and the dissolution due to better amorphization of the drug.

Baicalein-phospholipid complex: a novel drug delivery technology for phytotherapeutics.

Flavonoids are a group of low-molecular-weight polyphenolic compounds of plant origin. They exhibit a variety of biological activities such as anti-inflammatory, antioxidant, antiviral, and antitumor etc. Baicalein, is a bioactive flavone constituent of Scutellariae radix with a wide range of beneficial activities. But the poor solubility and dissolution rate limit its oral intestinal absorption and bioavailability. The aim of this study was to develop an amphiphilic phytophospholipid complex in order to enhance the delivery of poorly soluble drug (baicalein). The baicalein-phospholipid complex (Ba-PLc) was prepared and evaluated for various physico-chemical parameters like drug loading, infrared absorption (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffractometry (X-RPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. In the SEM, phospholipid complex (Ba-PLc) was found fluffy and porous with rough surface morphology. FT-IR, DSC and X-RPD data confirmed the formation of phospholipid complex. The water/ n-octanol solubility of baicalein was improved significantly in the complex. Improved dissolution was shown by the phospholipid complex. The results of the study concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the absorption and overall bioavailability of the baicalein molecule.

Rutin-phospholipid complex: an innovative technique in novel drug delivery system- NDDS.

Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs by influencing the dissolution and bioavailability. The aim of this study was to develop an amphiphilic phyto-phospholipid complex in order to enhance the delivery of poorly soluble rutin. The rutin-phospholipid complex (Ru-PLc) was prepared and investigated for various physico-chemical parameters like drug loading, infrared absorption (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. The in vitro anti-oxidant activity was also studied. In the SEM, Ru-PLc was found fluffy and porous with rough surface morphology. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water/ noctanol solubility of rutin was improved from 2.88 to 45.71 µg/ ml and 68.17 to 245.18 µg/ ml, respectively in the complex. The improved dissolution was shown by the phospholipid complex at different pH buffers. The antioxidant activity indicated that, the bioactivity of rutin was maintained even after being complexed with the phospholipid. Based on the results, it can be concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the overall absorption and bioavailability of the rutin molecule.

Quercetin-phospholipid complex: an amorphous pharmaceutical system in herbal drug delivery.

Development of amphiphilic drug-lipid complexes is a potential approach for improving therapeutic efficacy of the drugs by increasing solubility, release profile and oral bioavailability. Quercetin (3, 3', 4', 5, 7-pentahydroxyflavone), a polyphenolic flavonoid, shows several biological effects like anti-inflammatory, anti-cancer, antiproliferative, antimutagenic and apoptosis induction but its use is limited due to its low aqueous solubility. To overcome this limitation, a value added phospholipid complex of quercetin was developed to improve its aqueous solubility for better absorption through the gastrointestinal tract and this might result in improved bioavailability. The quercetin-phospholipid complex thus prepared was evaluated for various physico-chemical parameters like infra red spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM) and solubility study. The In vitro antioxidant activity was also studied. The phospholipid complex of quercetin was found to be fluffy and porous with rough surface in SEM. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water solubility of quercetin was improved by 12 folds (from 3.44 µg/ ml to 36.81 µg/ ml) in the prepared complex. There was no statistical difference between the quercetin complex and quercetin in the In vitro anti-oxidant activity, indicating that the process of complexation did not adversely affect the bioactivity of the active ingredient.

Hair growth and rejuvenation: an overview.

Hair has psychological and sociological importance throughout the ages in framing the personality and general appearance of an individual. Significant progress is being made on discovering an effective and safe drug for hair growth. Angiogenesis, androgen antagonism, vasodilation, potassium channel opening and 5-alpha reductase inhibition are the major non-surgical therapeutic strategies of hair growth promotion. In spite of a flood of drugs claiming to be useful as hair growth promoters, more rational strategies, which can target the problem areas or stages of the hair growth cycle effectively, are still awaited. This article highlights the developments in hair rejuvenation strategies and reviews the potential of herbal drugs as safer and effective alternatives.

Techniques for the discovery and evaluation of drugs against alopecia.

INTRODUCTION: Hair care, color and style play an important role in physical appearance and self-perception. Hair loss or alopecia is a common dermatological and affective disorder. Factors contributing to alopecia include genetic predisposition, hormonal factors, disease status, side effects of chemotherapeutic agents and stress. To keep pace with the demand for drugs for alopecia, attempts are being made to explore drugs with hair-growth-promotion activity. To explore and evaluate these, it is necessary to be familiar with the basics and the availability and suitability of techniques and experimental models of hair growth activity assessment. AREAS COVERED: Basic and advanced techniques and models for assessing hair growth activity. A variety of pharmacological models of hair growth are reviewed. This review will help in selecting a suitable, relevant, inexpensive, easy and reliable model for hair growth assessment. EXPERT OPINION: There is a need to identify the genes involved in hair follicle growth for the production of more effective animal models of the disorder. Standardization of pharmacological models will also be essential for better comparison and validation of results. Recently developed hair follicle organ culture models are a suitable, relevant and inexpensive alternative to traditional whole-animal pharmacological models and will, largely, replace whole-animal systems in the future.

Formulation and evaluation of mucoadhesive buccal films of enalapril maleate.

Enalapril maleate is used in the treatment of hypertension and angina pectoris. It shows low bioavailability due to high hepatic first pass metabolism. Hence the present work was undertaken to formulate mucoadhesive buccal films of enalapril maleate with an objective to improve therapeutic efficacy, patient compliance and the bioavailability. In the present study ten formulations of mucoadhesive drug delivery system of enalapril maleate were prepared as buccal films, by solvent casting technique. Sodium carboxymethylcellulose, hydroxylpropylmethylcellulose, hydroxyethylcellulose and polyvinyl pyrrolidone K-90 were used as mucoadhesive polymers. Prepared films were evaluated for their weight, thickness, surface pH, swelling index, drug content uniformity, in vitro residence time, folding endurance in vitro release and permeation studies. Films exhibited controlled release over more than 10 h in permeation studies. It was concluded that the films containing 20 mg of enalapril maleate in sodium carboxymethylcellulose 2% w/v and hydroxyethyl cellulose 2% w/v (formulation F5), showed good swelling, a convenient residence time and promising controlled drug release, thus can be selected for the development of buccal film for effective therapeutic uses.

Development and evaluation of pharmacosomes of aceclofenac.

Pharmacosomes are amphiphilic lipid vesicular systems containing phospholipid complexes with a potential to improve bioavailability of poorly water soluble as well as poorly lipophilic drugs. To improve the water solubility, bioavailability and minimize the gastrointestinal toxicity of aceclofenac, its pharmacosomes were prepared. Aceclofenac was complexed with phosphatidylcholine (80%) in two different ratios (1:1 and 2:1) using conventional solvent evaporation technique. Pharmacosomes thus prepared were subjected to solubility and drug content evaluation, scanning electron microscopy, differential scanning calorimetry, X ray powder diffraction and in vitro dissolution study. Pharmacosomes of aceclofenac were found to be disc shaped with rough surface in scanning electron microscopy. Drug content was found to be 91.88% (w/w) for aceclofenac phospholipid complex (1:1) and 89.03% (w/w) aceclofenac-phospholipid complex (2:1). Differential scanning calorimetric thermograms and X ray powder diffraction datas confirmed the formation of phospholipid complex. Solubility and dissolution profile of the prepared complex was found to be much better than aceclofenac.

Supramolecular phospholipids-polyphenolics interactions: the PHYTOSOME strategy to improve the bioavailability of phytochemicals.

The poor and/or erratic oral bioavailability of polyphenolics can be improved using the PHYTOSOME delivery system, a strategy that enhances the rate and the extent of solubilization into aqueous intestinal fluids and the capacity to cross biomembranes. Phospholipids show affinity for polyphenolics, and form supramolecular adducts having a definite stoichiometry. This article reviews the preparation and characterization of PHYTOSOME complexes and their activity in various medicinal (cardiovascular, anti-inflammatory, hepatoprotective, anticancer) and cosmetic (skin aging) realms of application.

Semecarpus anacardium Linn.: A review.

Semecarpus anacardium Linn. (Family: Anacardiaceae), commonly known 'Ballataka' or 'Bhilwa', has been used in various traditional system of medicines for various ailments since ancient times. Its nuts contain a variety of biologically active compounds such as biflavonoids, phenolic compounds, bhilawanols, minerals, vitamins and amino acids, which show various medicinal properties. The fruit and nut extract shows various activities like antiatherogenic, antiinflammatory, antioxidant, antimicrobial, anti-reproductive, CNS stimulant, hypoglycemic, anticarcinogenic and hair growth promoter. The article reviews the various activities of the plant.

Development and physicochemical evaluation of pharmacosomes of diclofenac.

Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80%) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 +/- 1.1%. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 microg mL-1 as compared to 10.5 microg mL-1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8% while the free diclofenac acid showed a total of only 60.4% drug release at the end of 10 h of dissolution study.

Pharmacosomes: the lipid-based new drug delivery system.

Lipid-based drug delivery systems have been investigated in various studies and shown their potential in controlled and targeted drug delivery. Pharmacosomes are amphiphilic phospholipid complexes of drugs bearing active hydrogen that bind to phospholipids. Pharmacosomes impart better biopharmaceutical properties to the drug, resulting in improved bioavailability. Pharmacosomes have been prepared for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. Developing the pharmacosomes of the drugs has been found to improve the absorption and minimize the gastrointestinal toxicity. This article reviews the potential of pharmacosomes as a controlled and targeted drug delivery system and highlights the methods of preparation and characterization.

Formulation and characterization of mucoadhesive buccal films of glipizide.

Mucoadhesive buccal films of glipizide were prepared by solvent casting technique using hydroxypropylmethylcellulose, sodium carboxymethylcellulose, carbopol-934P and Eudragit RL-100. Prepared films were evaluated for weight, thickness, surface pH, swelling index, in vitro residence time, folding endurance, in vitro release, permeation studies and drug content uniformity. The films exhibited controlled release over more than 6 h. From the study it was concluded that the films containing 5 mg glipizide in 4.9% w/v hydroxypropylmethylcellulose and 1.5% w/v sodium carboxymethylcellulose exhibited satisfactory swelling, an optimum residence time and promising drug release. The formulation was found to be suitable candidate for the development of buccal films for therapeutic use.

Iontophoretic drug delivery system: a review.

Among the recent developments in the field of transdermal drug delivery, iontophoresis has emerged as a very promising tool for this purpose. Various studies have been performed on drug delivery through the skin using electric current. Iontophoresis has thereby been found to be effective in particular in transdermal protein and peptide drug delivery. This article reviews the principle, potential benefits, and applications of drug delivery based on iontophoresis. It focuses furthermore on current research and future trends in the field of iontophoretic drug delivery.