Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.

Novel Formulation of Fusidic Acid Incorporated into a Myrrh-Oil-Based Nanoemulgel for the Enhancement of Skin Bacterial Infection Treatment.

Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box−Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.

Brucine-Loaded Ethosomal Gel: Design, Optimization, and Anti-inflammatory Activity.

Brucine, one of the natural medications obtained from Nux vomica seeds, is used as an anti-inflammatory drug. Several investigations were performed to overcome its drawbacks, which will affect significantly its pharmaceutical formulation. The goal of the current investigation was to design, optimize, and evaluate the anti-inflammatory performance of BRU ethosomal gel. Brucineethosomal formulations were prepared using thin film hydration method and optimized by central composite design approach using three independent variables (lecithin concentration, cholesterol concentration, and ethanol percentage) and three response variables (vesicular size, encapsulation efficiency, and skin permeation). The optimized formulation was examined for its stability and then incorporated into HPMC gel to get BRU ethosomal gel. The obtained BRU-loaded ethosomal gel was evaluated for its physical properties, in vitro release, and ex vivo permeation and skin irritation. Finally, carrageenan-induced rat hind paw edema test was adopted for the anti-inflammatory activity. The developed BRU ethosomal gel exhibited good physical characteristics comparable with the conventional developed BRU gel. In vitro release of BRU from ethosomal gel was effectively extended for 6 h. Permeation of BRU from ethosomes was significantly higher than all formulations (p < 0.05), since it recorded steady state transdermal flux value 0.548 ± 0.03 µg/cm2 h with enhancement ratio 2.73 ± 0.23. Eventually, BRU ethosomal gel exhibited potent anti-inflammatory activity as manifested by a significant decrease in rat hind paw inflammation following 24 h. In conclusion, the study emphasized the prospective of ethosomal gel as a fortunate carrier for intensifying the anti-inflammatory effect of Brucine.

Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology.

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles.

The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.

Dual-targeting potential of active constituents of Nigella sativa against FimH and CTX-M-15: A plausible therapeutic strategy against drug-resistant uropathogenic strains.

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during 10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.