Cubosomal nanoformulation increase invitro dissolution and anticancer activity of Fisetin in A549 lung cancer cells.

Aim: To prepare fisetin (FIS) cubosomal nanoformulation to increase aqueous solubility and anticancer activity. Methods: Top-down method using glyceryl monooleate (GMO) and Pluronic F-127. Results: Optimized using 2% GMO and 1% Pluronic F-127, reported 93.07 nm particle size, 80.10% drug entrapment, and reports more than 50% enhanced in vitro drug release than native FIS. MTT assay reports IC50 Values of FIS 16.59 µg/ml and optimized cubosomal FIS nanoformulation (FISCUB) 12.18 µg/ml. The colony numbers observed in clonogenic assay for FISCUB were 8.33 ± 0.58 and FIS 11.67 ± 1.15. In flow cytometry study, apoptotic cells in FISCUB and FIS-treated A549 cells were found to be 33.4 and 6.83% respectively. Conclusion: A stable cubosomal nanoformulation of FIS showed enhanced aqueous solubility and anticancer activity.

Formulation and Development of a Herbal Antifungal Gel Containing Origanum vulgare and Syzygium aromaticum Essential Oils Against Oral Candida albicans.

Background Oral candidiasis is the most prevalent oral fungal infection, and existing antifungal agents have side effects such as drug intolerance, resistance, and toxicity. Herbal essential oils are emerging as an alternative therapeutic approach for treating fungal infections. Origanum vulgare (O. vulgare), commonly known as oregano, and Syzygium aromaticum (S. aromaticum), commonly known as clove, are known to have antifungal properties and are effective against fluconazole-resistant strains. A combination of essential oils has a synergistic effect and aids in achieving effective antifungal activity at sufficiently low concentrations, which could lead to reduced side effects and resistance. Aim of the study This study aimed to formulate and develop an herbal antifungal gel containing O. vulgare and S. aromaticum and evaluate its synergistic antifungal efficacy against oral Candida albicans (C. albicans). Methodology Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determinations of O. vulgare and S. aromaticum essential oils were performed individually and in combination to assess the antifungal activity against C. albicans. Based on the obtained MIC and MFC of essential oils in combination, an herbal antifungal gel was formulated. Further, to determine the biocompatible nature of the gel, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. Results We found that a combination of O. vulgare and S. aromaticum essential oils showed antifungal activity at a lesser concentration, with a MIC of 0.19 µl/ml and MFC of 0.39 µl/ml when compared to their individual concentrations. Based on our results, an antifungal herbal gel comprising a concentration of 0.6 µl/ml of both essential oils was developed to achieve synergistic antifungal activity against oral C. albicans. The MTT assay of the herbal gel did not show any cytotoxicity. Conclusion The novel herbal antifungal gel containing O. vulgare and S. aromaticum is biocompatible in nature and provides an alternative therapeutic approach for treating oral candidiasis.

Current Novel Drug Deliveries for Oral Cancer: A Chronotherapeutic Approach.

Oral squamous cell carcinoma is a malignant disease that is causing considerable mortality worldwide. Conventional treatment approaches, like surgery, cause destructive alterations in facial appearance and oral function impairments associated with psychological and social functioning. Chemotherapy exhibits low bioaccessibility of the anticancer drugs, multiple drug resistance, higher dose necessities, which elevate toxicities to the normal cells, low therapeutic index, and non-specific targeting. Radiation therapies significantly affect the well-being of the patient and impair the quality of life. Therefore, chemotherapeutics are developed that can either actively or passively target the carcinomas, reduce the adverse side effect, and improve therapeutic efficacy. Innovations in novel drug delivery systems deliver the drugs to the desired site of action with better treatment approaches with reduced toxicities to the normal cells and improve the health and survival rate of the patient. Cancer chronotherapy enhances the treatment proficiency by administration of the drugs at the best time, considering biological timings to improve the treatment profiles. Chronotherapy provides benefits to the current anticancer therapies, with minimum adverse effects to the healthy cells. This review discusses the risk factors for oral carcinomas, targeted therapy by nanocarriers, nanotechnology approaches, the role of circadian rhythm in the management of oral cancer, and advances in controlled drug delivery.

Formulation and Evaluation of Resveratrol Loaded Cubosomal Nanoformulation for Topical Delivery.

AIM: The aim of the study was to formulate, characterize, and evaluate the Resveratrol- loaded Cubosomes (RC) for topical application. BACKGROUND: Resveratrol (RV) is a nutraceutical compound with exciting pharmacological potential in different diseases, including cancers. Many studies on resveratrol have been reported for anti- melanoma activity. Due to its low bioavailability, the therapeutic activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been made to increase its activity through transdermal drug delivery. OBJECTIVE: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate Resveratrol-loaded Cubosomal Gel (RC-Gel) for its topical application. METHODS: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. RESULTS: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV, respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 3.91%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. CONCLUSION: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

A validated stability-indicating HPLC method for simultaneous estimation of resveratrol and piperine in cubosome and human plasma.

Resveratrol and piperine are proven for their therapeutic benefits to treat various diseases. Due to their synergistic actions and combined drug delivery application, a rapid and specific RP-HPLC method was developed and validated as per ICH guidelines, by using an isosbestic point. The chromatographic separation was performed with Luna 5 µ 100 ŠC-18(2) HPLC column by using acetonitrile (ACN): phosphate buffer (0.01% orthophosphoric acid) (55:45) as mobile phase, at 1 mL/min of flow rate and 330 nm. The developed method was found to be linear over the concentration range of 0.25-8 µg/mL with correlation coefficient value >0.999. The developed method was accurate (percent recovery 98.06-101.74%), precise (percent relative standard deviation <2.0%), and robust. The limit of detection and limit of quantification for resveratrol were found to be 0.02 and 0.08 µg/mL, respectively and 0.04 and 0.11 µg/mL, for piperine, respectively. The developed method was also validated in human plasma as per ICH guidelines. Moreover, stress degradation studies of both phytoconstituents were studied and the relevancy of the developed method was analyzed on cubosome nanoformulation. A good separation of drug peaks was observed in the presence of the degradation products. This method could thus be used for regular in vitro and in vivo estimation of piperine and resveratrol.