Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, in-vitro, ex-vivo, and in-vivo analyses.

BACKGROUND: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles. METHODS: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties. RESULTS: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency values of 270 ± 27.4 nm, -23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope. In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones. CONCLUSION: Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

Physicochemical, rheological and antifungal evaluation of miconazole nitrate organogels for topical delivery.

Topical preparations have a problem of being wiped off after a short time, which results in low activity of the active moiety. In this research, topical organogels (OGs) were prepared with different oils for the controlled action of miconazole nitrate. Various oils were checked for their gel-forming ability. Controlled release OGs were prepared with a 15% concentration of glyceryl monostearate. Differential scanning calorimetry was performed to study the thermal behavior of gels. X-ray diffraction revealed that the drug was changed into an amorphous form from the crystalline form. The absence of any interaction between the active ingredient and excipients was concluded by Fourier Transform Infrared spectroscopy. Permeability studies were carried out with cellulose acetate membrane by using Franz diffusion cell containing phosphate buffer saline pH 7.4. The release of drug followed the Weibull model. A frequency sweep test was performed to study the rheological behavior of optimized formulations. Rheology revealed the true nature of formulations whether they are gels or just viscous fluids. Images of scanning electron microscopy showed a network formed by the gelator molecules. The antifungal activity was checked against C. albicans and A. niger and it was best by the formulation made by TT. It was concluded that all the OGs gave controlled topical antifungal action.

Hepatoprotective and Renoprotective Properties of Lovastatin-Loaded Ginger and Garlic Oil Nanoemulsomes: Insights into Serum Biological Parameters.

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.

An assessment of bioavailability of acrylate based pH-sensitive complexes of lovastatin.

Lovastatin (LSN), a potent anti-hyperlipidemic drug, possesses poor bioavailability due to its very low aqueous solubility. The objective of this study was to establish a relationship between increased drug solubility before reaching site of absorption or increasing drug solubility at target absorption site for accentuated bioavailability of LSN. Composites of LSN with oppositely natured pH-sensitive acrylate polymers, cationic Eudragit EPO (EPO) and anionic Eudragit L100 (L100), were fabricated with physical trituration and kneading methods. Formulations were characterized for solubility, FTIR, PXRD, DSC, SEM, dissolution and bioavailability studies in rats. Interestingly, we observed that physical mixtures of EPO outmatched its kneaded formulations, whereas the physical mixtures and kneaded dispersions of L100 were virtually similar in characteristics. EPO was superior in boosting LSN solubility in the respective medium than the L100. Moreover, EPO produced immediate release profile in gastric environment whereas L100 offered sustained release of LSN in intestinal milieu. Bioavailability studies in rats further supported the EPO formulation in terms of shorter Tmax, higher Cmax and heightened AUC.

Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis.

Flurbiprofen, an NSAID, is a water insoluble drug that is also notorious for gastric irritation and inflammation. This study was aimed at using a natural gastrprotective oil as the internal phase to develop flurbiprofen micro emulsion (ME) to improve it solubility and ameliorate its gastric side effects. Upon screening of ME components for drug solubility, clove oil, tween 80 and transcutol were identified as the oil, surfactant and co surfactant, respectively, with higher flurbiprofen solubility. Pseudo-ternary phase diagrams revealed that the ME made with surfactant only and without co-surfactant displayed the similar ME region as made with the mixture of surfactant and co-surfactant. Furthermore, drug loaded oil was also used to draw pseudo-ternary phase diagram and a very little decrease in the ME region was observed. Therefore, co-surfactant free flurbiprofen loaded ME was developed to avoid side effects associated with the use of excessive surfactant quantities. ME were found to possess size in the range of 11-41 nm with PDI <0.5 and a slightly negative charge. Conductivity, pH and refractive indices of the selected MEs were well in the range. Drug release studies indicated maximum drug release from MEs within 5 min. Analysis of the gastric mucosa of rats after oral administration of drug solution and drug loaded ME confirmed that clove oil based ME provided significant protection against the NSAIDs induced gastric damage.