Tailoring of Novel Bile Salt Stabilized Vesicles for Enhanced Transdermal Delivery of Simvastatin: A New Therapeutic Approach against Inflammation

Abstract

Simvastatin (SMV), a cholesterol-lowering agent, has antioxidant and anti-inflammatory effects. Nevertheless, the oral use of SMV is linked with poor systemic bioavailability owing to its limited aqueous solubility and extensive first-pass metabolism. The aim of this study was to evaluate the feasibility of transdermal delivery of SMV using bile salt stabilized vesicles (bilosomes) for enhancing the anti-inflammatory potential of SMV. SMV-loaded bilosomes (SMV-BS) were prepared by the thin film hydration technique and optimized by 33 Box–Behnken design. The fabricated SMV-BS were assessed for vesicle size, entrapment efficiency (% EE) and cumulative drug release. The optimized formula was incorporated into HPMC gel and investigated for physical properties, ex vivo permeation, in vivo pharmacokinetic study and anti-inflammatory potential in inflamed paw edema rat model. The optimized SMV-BS showed vesicle size of 172.1 ± 8.1 nm and % EE of 89.2 ± 1.8%. In addition, encapsulating SMV within bilosomal vesicles remarkably sustained drug release over 12 h, compared to plain drug suspension. Furthermore, SMV-loaded bilosomal gel showed a three-fold enhancement in SMV transdermal flux, compared to plain drug suspension. Most importantly, the relative bioavailability of SMV-BS gel was ~2-fold and ~3-fold higher than those of oral SMV suspension and SMV gel, respectively. In carrageenan-induced paw edema model, SMV-BS gel induced a potent anti-inflammatory effect, as evidenced by a remarkable reduction in paw edema, which was comparable to that of the standard anti-inflammatory drug, indomethacin. Collectively, bilosomes might represent a plausible transdermal drug delivery system that could enhance the anti-inflammatory activity of SMV by boosting its skin permeation and its systemic bioavailability.

Tailoring of Bilosomal Nanogel for Augmenting the Off-Label Use of Sildenafil Citrate in Pediatric Pulmonary Hypertension

“…The %EE of F14 and F3 were 78.1 ± 1.4 and 69.3 ± 1.1%, respectively. Similar results were reported by Khafagy and his colleagues who verified a mutual increment in the entrapment of simvastatin within nanobilosomal vesicles with an increase in lipid concentration from 1 to 3% . On the same context, the Span 60 concentration exerted a synergistic effect on the EE% of SDF within bilosomes.…”

“…Zeta potential is another crucial parameter that measures the strength of the attraction/repulsion between adjacent particles and, thereby, offers information on the physical stability of the produced bilosomal formulations. Generally, in colloidal dispersion, a zeta potential of ±20 mV is required for ensuring electrostatic colloidal stability . The ZP value of the optimized formula was −20.4 ± 1.1 mV (Figure B), suggesting the high physical stability of the formulated bilosomes.…”

“…Generally, in colloidal dispersion, a zeta potential of ±20 mV is required for ensuring electrostatic colloidal stability. 30 The ZP value of the optimized formula was −20.4 ± 1.1 mV (Figure 3B), suggesting the high physical stability of the formulated bilosomes.…”

“…Bilosomes, bile salts-stabilized vesicles, are a relatively new lipid-based vesicular system that is made of a nonionic surfactant; they resemble niosomes but with the inclusion of bile salts in their structure. , Bilosomes elicited a significant advance in oral vaccine delivery because they are less susceptible to degradation by gastric enzymes as well as acids . Furthermore, bilosomes have been recently adopted for transdermal drug delivery . The nanosized range of bilosomes along with the presence of negatively charged bile salts (sodium deoxycholate) significantly supports the skin permeability of the drug and enhances the stability of the formed bilosomes, respectively.…”

In Vitro Characterizations of Post-Crosslinked Gelatin-Based Microspheres Modified by Phosphatidylcholine or Diammonium Phosphate as Antibiotic Delivery Vehicles

“…Therefore, some researchers began to study drug carriers for controlled drug release [ 1 , 2 ]. In this method, the drug can be released directly and locally through the drug carrier, which can control the drug release concentration and avoid the loss caused by a large number of passages and metabolism after delivery [ 3 , 4 ].…”