Critical Review on Balanites aegyptiaca Delile: Phytoconstituents, Pharmacological Properties and Nanointerventions.

Balanites aegyptiaca Delile (BA) is an enduring xerophytic woody and spinous flowering tree and is commonly known as desert date or Ingudi (Hingot). It belongs to the family Zygophyllaceae, which is specific to be drought areas of Nigeria, Africa, South Asia and India (Rajasthan). In Ayurveda, this traditional medicinal plant is reported for the management of jaundice, syphilis, yellow fever, metabolic disorders, liver, and spleen problems. The main aim of the review is to compile its medicinal uses and further advancements to showcase the promises inherited in various parts of the plant for the benefit of mankind. As per the literature survey, various researchers have focused on the detailed investigation of BA including the phytopharmacological evidence, chemical constituents, nano-formulations, commercialized products, and clinical trials. Several remarkable scaffolds and isolated compounds like diosgenin, yamogenin, balanitin1/2, balanitin 3, bal4/5, bal6/7, rutin-3-glycosides, 3,7-diglycosides, (3, 12, 14, 16)-(12-hydroxycholest-5-ene-3,16-diyl-bis)-D-glucopyranoside and balanitoside have been identified. Additionally, this traditional plant has been scientifically proven by in vitro and in vivo. Based on the complete review of this plant, most of the compounds have been isolated from the fruit and kernel part. Additionally, based on the literature, a histogram was developed for pharmacological activity in which antidiabetic study was found to be more compared to other pharmacological activity. As a spinous desert dates, this plant needs to be explored more to bring out newer phytochemicals in the management of various diseases.

Selenium-Based Novel Epigenetic Regulators Offer Effective Chemotherapeutic Alternative with Wider Safety Margins in Experimental Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Despite the critical involvement of epigenetic modifications in CRC, the studies on the chemotherapeutic efficacy of various epigenetic regulators remain limited. Considering the key roles of histone deacetylases (HDACs) in the regulation of diverse cellular processes, several HDAC inhibitors are implied as effective therapeutic strategies. In this context, suberoylanilide hydroxamic acid (SAHA), a 2nd-generation HDAC inhibitor, showed limited efficacy in solid tumors. Also, side effects associated with SAHA limit its clinical application. Based on the redox-modulatory and HDAC inhbitiory activities of essential trace element selenium (Se), the anti-carcinogenic potential of Se substituted SAHA, namely, SelSA-1 (25 mg kg-1), was screened for it enhanced anti-tumorigenic role and wider safety profiles in DMH-induced CRC in Balb/c mice. A multipronged approach such as in silico, biochemical, and pharmacokinetics (PK) has been used to screen, characterize, and evaluate these novel compounds in comparison to existing HDAC inhibitor SAHA. This is the first in vivo study indicating the chemotherapeutic potential of Se-based novel epigenetic regulators such as SelSA-1 in any in vivo experimental model of carcinogenesis. Pharmcological and toxicity data indicated better safety margins, bioavailability, tolerance, and elimination rate of SelSA-1 compared to classical HDAC inhibitor SAHA. Further, histological and morphological evidence demonstrated enhanced chemotherapeutic potential of SelSA-1 even at lower pharmacological doses than SAHA. This is the first in vivo study suggesting Se-based novel epigenetic regulators as potential chemotherapeutic alternatives with wider safety margins and enhanced anticancer activities.

Recent update on nano-phytopharmaceuticals in the management of diabetes.

Due to changed lifestyle and other reasons, diabetes has become one of the common metabolic disorder of the globe. Numerous therapeutic options are available, which controls the plasma glucose levels. However, most of the drugs are associated with some undesired side effects. Owing to the side effects and enhanced understanding of the phytochemicals, an inclination toward herbal medicine is seen in the population. These herbal products are also associated with concerns like poor aqueous solubility, compromised permeation, and a low degree of bioavailability. So, the emergence of nanotechnology in the herbal medicine is required to nullify the associated concerns of conventional antidiabetic drugs. The present review aims to compile the literature available for the nano-interventions pertinent to herbal products for diabetes management.

Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis.

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

Aceclofenac cocrystal nanoliposomes for rheumatoid arthritis with better dermatokinetic attributes: a preclinical study.

AIM: The aim of present research was to complex aceclofenac with lysine (LYS) and the developed aceclofenac-LYS cocrystal was encapsulated in lipid bilayers of liposomes by employing dual carrier approach for the treatment of pain-related disorders in rheumatoid arthritis (RA). MATERIALS & METHODS: The developed carriers were characterized for particle size, drug release, ex vivo and in vivo studies, dermatokinetic modeling, complete freund's adjuvant (CFA)-induced RA rat model, radiant heat tail-flick method, formalin-induced paw-licking model, paw edema model and xylene-induced ear edema model in mice. RESULTS: The developed nanoliposomes offered nanometric size, controlled drug release and enhanced drug permeation. Further, hydrogel incorporated nanoproduct was found to be rheologically acceptable and substantially compatible with rodent skin. CONCLUSION: The studies indicated the superiority of LYS-conjugated liposome-entrapped nanocarriers for improved management of conditions like RA over the marketed product.

PLGA-soya lecithin based micelles for enhanced delivery of methotrexate: Cellular uptake, cytotoxic and pharmacokinetic evidences.

Biocompatible and biodegradable polymers like PLGA have revolutionized the drug delivery approaches. However, poor drug loading and substantially high lipophilicity, pave a path for further tailing of this promising agent. In this regard, PLGA was feathered with biocompatible phospholipid and polymeric micelles were developed for delivery of Methotrexate (MTX) to cancer cells. The nanocarriers (114.6nm±5.5nm) enhanced the cytotoxicity of MTX by 2.13 folds on MDA-MB-231 cells. Confocal laser scanning microscopy confirmed the increased intracellular delivery. The carrier decreased the protein binding potential and enhanced the bioavailable fraction of MTX. Pharmacokinetic studies vouched substantial enhancement in AUC and bioresidence time, promising an ideal carrier to effectively deliver the drug to the site of action. The developed nanocarriers offer potential to deliver the drug in the interiors of cancer cells in an effective manner for improved therapeutic action.

Novel phospholipid-based topical formulations of tamoxifen: evaluation for antipsoriatic activity using mouse-tail model.

OBJECTIVE: Tamoxifen (TAM) is widely employed in the treatment of breast malignancies and is also found to be effective in psoriasis treatment. The current studies aimed to explore the antipsoriatic potential of topical TAM encapsulated in the new generation phospholipid-based vesicular and micellar systems, i.e. flexible membrane vesicles (FMVs) and pluronic lecithinized organogels (PLOs). METHODS: TAM-loaded-FMVs were prepared by thin-film hydration technique, while TAM-PLOs were prepared by simple mixing. Mouse-tail model was used to evaluate the antipsoriatic activity of the novel formulations. The mouse tails were treated once-a-day with different formulations for a period of four weeks and prepared for longitudinal histological sections by hematoxylin-eosin staining technique. The length of the orthokeratotic regions in stratum granulosum was measured on 10 sequential scales per tail section as percentage of the full length of the scale, and the drug activity was calculated further. RESULTS: Evaluation of antipsoriatic activity on mice tail revealed significantly higher (p < 0.01) efficacy of TAM-FMV gel (i.e. 35.8%) and TAM-PLO (i.e. 24.6%) vis-à-vis the conventional TAM-hydrogel (i.e. 10.2%). CONCLUSIONS: The results of these studies demonstrated immense potential of the topically applied TAM-encapsulated vesicular and micellar systems in psoriasis, thus calling for more comprehensive investigations to establish the role of TAM in the management of psoriasis.

Tamoxifen-loaded lecithin organogel (LO) for topical application: Development, optimization and characterization.

Lecithin organogels (LOs) are semi-solid systems with immobilized organic liquid phase in 3-D network of self-assembled gelators. This paper attempts to study the various attributes of LOs, starting from selection of materials, optimization of influential components to LO specific characterization. After screening of various components (type of gelators, organic and aqueous phase) and construction of phase diagrams, a D-optimal mixture design was employed for the systematic optimization of the LO composition. The response surface plots were constructed for various response variables, viz. viscosity, gel strength, spreadability and consistency index. The optimized LO composition was searched employing overlay plots. Subsequent validation of the optimization study employing check-point formulations, located using grid search, indicated high degree of prognostic ability of the experimental design. The optimized formulation was characterized for morphology, drug content, rheology, spreadability, pH, phase transition temperatures, and physical and chemical stability. The outcomes of the study were interesting showing high dependence of LO attributes on the type and amount of phospholipid, Poloxamer™, auxillary gelators and organic solvent. The optimized LO was found to be quite stable, easily applicable and biocompatible. The findings of the study can be utilized for the development of LO systems of other drugs for the safer and effective topical delivery.

Novel dithranol phospholipid microemulsion for topical application: development, characterization and percutaneous absorption studies.

The objective of this study was to develop and characterize a novel dithranol-containing phospholipid microemulsion systems for enhanced skin permeation and retention. Based on the solubility of dithranol, the selected oils were isopropyl myristate (IPM) and tocopherol acetate (TA), and the surfactants were Tween 80 (T80) and Tween 20 (T20). The ratios of cosurfactants comprising of phospholipids and ethanol (1 : 10) and surfactant to co-surfactant (1 : 1 and 2.75 : 1) were fixed for the phase diagram construction. Selected microemulsions were evaluated for globule size, zeta potential, viscosity, refractive index, per cent transmittance, stability (freeze thaw and centrifugation), ex vivo skin permeation and retention. The microemulsion systems composed of IPM and T80 with mean particle diameter of 72.8 nm showed maximum skin permeation (82.23%), skin permeation flux (0.281 mg/cm²/h) along with skin retention (8.31%) vis-à-vis systems containing TA and T20. The results suggest that the developed novel lecithinized microemulsion systems have a promising potential for the improved topical delivery of dithranol.

Phospholipid-based formulation with improved attributes of coal tar.

PURPOSE: The aim of this study was to evaluate the formulation characteristics and pharmacodynamic activity of the lecithinized coal tar formulation (LCT) employing different methodologies and compare it with that of a conventional coal tar formulation (CCT) employing different methodologies. METHODS: Characterization for skin-staining was carried out employing shaved back skin of rats. Rheological properties were determined using Texture Analyzer. The dispersibility of the coal tar formulations in water was determined by macroscopic examination. Antipsoriatic pharmacodynamic activity of the formulations was evaluated employing mouse-tail model. RESULTS: The study revealed distinct superiority of the LCT vis-à-vis CCT. The LCT was found be nonstaining with no apparent adverse effect on rat skin. Rheological studies revealed significantly better spreadability and lower stickiness of the LCT than that of CCT. The LCT forms uniform dispersion with water, while the CCT tends to form large aggregates. Finally, the pharmacodynamic model demonstrated superior anti-psoriatic activity of the LCT. CONCLUSIONS: The findings with the LCT were highly encouraging, as it proved to be nonstaining to skin, easily applicable, and water dispersible with markedly improved efficacy. The product was thus potentially more patient-compliant and efficacious. The evaluation methodologies adopted during the studies were found to be accurate, simple, specific, and reproducible with immense potential for assuring the quality of coal tar product(s).