Fabrication and Appraisal of Simvastatin via Tailored Niosomal Nanovesicles for Transdermal Delivery Enhancement: In Vitro and In Vivo Assessment

Abstract

Simvastatin (SIM) is a HMG-CoA reductase inhibitor employed in the management of hyperlipidemia. However, its low bioavailability limits its clinical efficacy. The objective of this study was to overcome the poor bioavailability of SIM via the transdermal application of a SIM-loaded niosomal gel. Niosomes loaded with SIM were fabricated by means of the thin-film hydration method and optimized through a 33-factorial design utilizing Design Expert® software. The prepared niosomes were evaluated for entrapment efficiency (EE%), zeta potential, vesicle size, and cumulative percentage of drug release. The optimum niosomal formulation was loaded on the gel and evaluated for physical properties such as color, clarity, and homogeneity. It was also evaluated for spreadability, and the cumulative % drug release. The best niosomal gel formula was appraised for ex vivo permeation as well as pharmacokinetic study. The SIM-loaded niosomes showed EE% between 66.7–91.4%, vesicle size between 191.1–521.6 nm, and zeta potential ranged between −0.81–+35.6 mv. The cumulative percentage of drug released was ranged from 55% to 94% over 12 h. SIM-loaded niosomal gels were clear, homogenous, spreadable, and the pH values were within the range of physiological skin pH. Furthermore, about 73.5% of SIM was released within 24 h, whereas 409.5 µg/cm2 of SIM passed through the skin over 24 h in the ex vivo permeation study. The pharmacokinetic study revealed higher AUC0–∞ and Cmax with topical application of SIM-loaded niosomal gel compared to topical SIM gel or oral SIM suspension. The topical application of SIM-loaded niosomal gel ascertained the potential percutaneous delivery of SIM.

Formulation and Evaluation of Niosomal Alendronate Sodium Encapsulated in Polymeric Microneedles: In Vitro Studies, Stability Study and Cytotoxicity Study

“…The charged particles repel one another as the ZP increases, stabilizing the system against aggregation. Colloidal systems with a zeta potential of higher than +30 mV or lower than −30 mV are considered stable [ 31 , 32 ]. Here, the ZP values of all formulations were noted to be in the range of −27.6 ± 0.22 and −42.27 ± 2.25 mV, as shown in Table 3 , which is an indication of a stable system due to the electrostatic repulsion between nanovesicles [ 33 ].…”

A novel pH‐responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan‐based nanocarrier: Emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction

“…The zeta potential was +47 mV for the nanocarriers demonstrating good stability (Figure 6). 81 Also, the positive charge of niosomes improves their interaction with cell membranes 82 …”

Validated green spectroscopic manipulation of area under the curve (AUC) for estimation of Simvastatin: Application to nano-structured lipid carriers and niosomal systems

“…The first method was reported for the analysis of NLC of SIM using a stationary phase C18 coulumn and a mobile phase at a mixture of acetonitrile and 0.1% phosphoric acid (85:15, v/v) at pH 4 at flow rate of 1.5 mL/min and UV detection at 238 nm 47 . The second method was reported for the analysis of niosomal system of SIM using a stationary phase C18 coulumn and a mobile phase of acetonitrile and formic acid 3 mM (51:49 v/v) at flow rate of 1 mL/min and UV detection at 238 nm 48 .…”