Preparation and Optimization of In Situ Gel Loaded with Rosuvastatin-Ellagic Acid Nanotransfersomes to Enhance the Anti-Proliferative Activity

Abstract

The objective of this study was to develop an optimized sustained-release nanotransfersomes (NTS) based in situ gel formulation of rosuvastatin (RO) combined with ellagic acid (EA) antioxidant, to enhance cytotoxic and anti-proliferative activity against tongue carcinoma. The concentrations of lecithin, Tween 80, and d-tocopherol polyethylene glycol succinate (TPGS) were considered as independent variables. Particle size, entrapment, and stability were selected as dependent variables. The obtained formulation containing 25% lecithin, 20% Tween 80, and TPGS 15% fulfilled the prerequisites of the optimum formulation. RO-NTS loaded in situ gel was prepared and optimized for concentrations of Poloxamer 407, and Carbopol, using statistical design. Drug release from in situ gel showed a sustained release profile. The RO IC50 was decreased by half for the in situ gel in comparison to plain RO and RO-EA-NTS. A significant amount of caspase-3 was detected in all the formulation treatments. The studies indicated that EA's synergistic anti-oxidant effect owing to a high affinity to the PGP efflux transporter and higher penetration in the RO-NTS formulation led to a higher inhibition against human chondrosarcome-3 cancer cell lines. RO-EA NTS-loaded in situ gel had a sustained release that could be significant in localized therapy as an alternative to surgery in the treatment of aggressive tongue carcinoma. sensitivity of lung cancer and human leukemia cell lines to anthracyclines [6,7]. Administration of statins combined with antioxidant compounds of natural origin can yield better results as shown in the combination of simvastatin and alpha-lipoic acid that improved toxicity against breast carcinoma cell lines [8].Transferosomes, defined as vesicular colloidal dispersions composed mainly of phospholipids and nonionic surfactants acting as edge activators (EA), have attracted a great deal of attention in the field of drug delivery [9]. The presence of such EA weakens the bonds between phospholipids molecules and imparts the property of elasticity onto transferases making them ultra deformable vesicles. Transferosomes have several advantages that make them successful vesicular drug delivery systems, including (a) being biodegradable and biocompatible with human body, and (b) the ability of EA to solubilize and stabilize poorly soluble drugs owing to their surface activity, low toxicity, enhanced tissue targeting capacity, and ability to obtain prolonged drug release [10][11][12]. RO, also known as "superstatin," is the most effective antihyperlipidemic agent in the statins family. It is more efficient and attains fewer side effects compared to other statins although it exhibits poor solubility and poor bioavailability [13]. Several studies have proven the anticancer activity of RO. It showed cytotoxic effects against thyroid cancer cells in vitro as it increased the caspase-3 activity and apoptosis confirmed by DNA fragmentation analysis [14], and reduced viability in cervical, hepatic, and breast cancer cell lines [15]. Mor...

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Nasal Gel Loaded with Amphotericin Nanotransferosomes as Antifungal Treatment for Fungal Sinusitis

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Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance

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