Aceclofenac/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line.

Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.

Propranolol-Loaded Trehalosome as Antiproliferative Agent for Treating Skin Cancer: Optimization, Cytotoxicity, and In Silico Studies.

This study aims at preparing propranolol-loaded trehalosomes (a trehalose-coated liposome) to be used as an antiproliferative agent for treating skin cancer. A factorial design was used to select the optimum formula, where trehalose, lecithin, and Tween 80 levels were studied. A total of 24 runs were prepared and characterized according to size, charge, entrapment efficiency, and release after 3 h to select the optimum formula. The optimized formula was investigated using TEM, DSC, and FTIR. Cell studies were carried out against the human melanoma cell line to measure cytotoxicity, apoptosis/necrosis, and cell cycle arrest. In silico studies were conducted to understand the interaction between propranolol and the influential receptors in melanoma. The results showed the selected formula consisted of trehalose (175 mg), lecithin (164 mg), and Tween 80 (200 mg) with a size of 245 nm, a charge of -9 mV, an EE% of 68%, and a Q3 of 62%. Moreover, the selected formula has good cytotoxicity compared to the free drug due to the synergistic effect of the drug and the designed carrier. IC50 of free propranolol and the encapsulation of propranolol were 17.48 µg/mL and 7.26 µg/mL, respectively. Also, propranolol and the encapsulation of propranolol were found to significantly increase early and late apoptosis, in addition to inducing G1 phase cell cycle arrest. An in silico virtual study demonstrated that the highest influential receptors in melanoma were the vitamin D receptor, CRH-R1, VEGFR 1, and c-Kit, which matches the results of experimental apoptotic and cell cycle analysis. In conclusion, the selected formula has good cytotoxicity compared to the free drug due to the synergistic effect of the drug and the designed carrier, which make it a good candidate as an antiproliferative agent for treating skin cancer.

Enhanced bioavailability and pharmacokinetics parameters of Enalapril solid self nanoemulsifying oral dispersible tablet: formulation, in vitro and in vivo evaluation.

Enalapril (EN) is an antihypertensive drug that is sparingly soluble in water with limited oral bioavailability. Successfully prepared self-nanoemulsifying systems (SNES) loaded with EN were developed. The solubility of EN in different oils, surfactants, and cosurfactants was tested. Pseudoternary phase diagrams were developed, and various SNES formulations were prepared and evaluated regarding content uniformity, emulsification time, droplet size (DS), and zeta potential (ZP). The selected system was examined using transmission electron microscopy. Solid Self-Nanoemulsifying Systems (SSNES) were formulated using Avicel® PH101 carrier and Aerosil® 200 adsorbent to form a free-flowing powder. The powder was formulated as an oral disintegrating tablet (ODT) using superdisintegrants and tested for physicochemical properties and stability. Finally, an in vivo pharmacokinetic study in healthy human volunteers was carried out. The composition of the selected SNES was 10% Labrafil®, 60% Tween 80, and 30% Transcutol® HP. It developed with an emulsification time of 21 sec, DP range of 60.16 nm, ZP of 1.17 mV, and spherical-shaped globules. The accelerated stability testing proved that there was no significant difference in physical properties after storage for 3 months. The percentage of relative bioavailability for formula F2 was 112.04%. The results of this study proved that the prepared EN-SSNES ODT represents a novel formulation alternative to the currently marketed tablet.

Tenoxicam loaded hyalcubosomes for osteoarthritis.

The main aim is to develop transcutaneous tenoxicam (TNX) loaded vesicles to control osteoarthritis (OA) without common side effects. Different vesicles were prepared by the emulsification technique, where poloxamer and glyceryl monooleate used for cubosomes. Then, hyalcubosomes were prepared by adding sodium hyaluronate to cubosomes components. Different characterization techniques were used. The selected formulations were tested using an ex-vivo permeation study to evaluate the ability to penetrate and retained in skin layers. Also, in-vitro cell studies using human skin fibroblasts were evaluated the safety of the formulation. The anti-inflammatory efficiency was tested using an in-vivo carrageenan-induced rat paw edema model. Finally, the efficiency to control OA symptoms was tested on three patients with a medical history of knee OA. Results confirmed the successful development of spherical cubosomes with particle size <250 nm, -14.5 mV, high entrapment efficiency percentage (>90%). Moreover, the addition of sodium hyaluronate to selected cubosomes improved viscosity and spreadability. Permeation study confirmed drug penetration and deposition. Cell studies proved the safety of the selected formulation. The animal model showed high anti-inflammatory activity. Finally, the preliminary clinical study demonstrates the potential efficacy and safety of the formulation in controlling OA symptoms over 8 weeks of therapy.

Formulation and characterization of chlorhexidine HCl nanoemulsion as a promising antibacterial root canal irrigant: in-vitro and ex-vivo studies.

Introduction and aim: Chlorhexidine Hydrochloride [Chx.HCl] has a broad-spectrum antibacterial effect, sustained action and low toxicity so it has been recommended as a potential root canal irrigant. The aim of this study was to improve the penetration ability, cleansing and antibacterial effect of Chx.HCl using a newly formulated Chx.HCl nanoemulsion and use it as root canal irrigant. Methods: Chx.HCl nanoemulsions were prepared using two different oils; Oleic acid and Labrafil M1944CS, two surfactants; Tween 20 and Tween 80 and co-surfactant; Propylene Glycol. Pseudoternary phase diagrams were constructed to designate the optimum systems. The prepared nanoemulsion formulae were evaluated for their drug content, emulsification time, dispersibility, droplet size, in-vitro drug release, thermodynamic stability, In-vitro antibacterial activity and ex-vivo study for the selected formula. Comparisons were made of Chx.HCl nanoemulsion with two different concentrations 0.75% and 1.6% vs Chx.HCl normal particle size as root canal irrigant for their penetration ability, cleansing effect and antibacterial effect. Results: The selected formula was F6 with composition of 2% Labrafil, 12% Tween 80 and 6% Propylene glycol. It has small particle size (12.18 nm), short emulsification time (1.67 seconds), and fast dissolution rate after 2 minutes. It was found to be a thermodynamically/physically stable system. The higher concentration of Chx.HClnanoemulsion1.6% shows the best penetration ability compared to Chx.HCl normal particle size due to the smaller particle size. Chx.HCl nanoemulsion 1.6% has the lowest mean value of the remaining debris surface area (2001.47 µm2) when compared to normal particle size material (2609.56 µm2). Conclusion: Chx.HCl nanoemulsion preparation has better cleansing ability and antibacterial effect with high efficacy on Enterococcus faecalis, where high reduction rate or complete eradication of bacterial cells has been achieved.