Atorvastatin Calcium (At-Ca) has pleiotropic effect as anti-inflammatory drug beside its main antihyperlipidemic action. Our study was conducted to modulate the anti-inflammatory effect of At-Ca to be efficiently sustained for longer time. Single oil-water emulsion solvent evaporation technique was used to fabricate At-Ca into polymeric nanoparticles (NPs). In vitro optimization survey was performed on Poly(lactide-co-glycolide) (PLGA) loaded with At-Ca regrading to particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (% EE), surface morphology and in vitro release pattern. In vitro drug-polymers interactions were fully scanned using Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning calorimetry (DSC) proving that the method of fabrication is an optimal strategy maintaining the drug structure with no interaction with polymeric matrix. The optimized formula with particle size (248.2 ± 15.13 nm), PDI (0.126 ± 0.048), zeta potential (−12.41 ± 4.80 mV), % EE (87.63 ± 3.21%), initial burst (39.78 ± 6.74%) and percent cumulative release (83.63 ± 3.71%) was orally administered in Male Sprague–Dawley rats to study the sustained anti-inflammatory effect of At-Ca PLGA NPs after carrageenan induced inflammation. In vivo results demonstrate that AT-Ca NPs has a sustained effect extending for approximately three days. Additionally, the histological examination revealed that the epidermal/dermal layers restore their typical normal cellular alignment with healthy architecture.
Zaleplon (ZP) is a sedative and hypnotic drug used for the treatment of insomnia. Despite its potent anticonvulsant activity, ZP is not commonly used for the treatment of convulsion since ZP is characterized by its low oral bioavailability as a result of poor solubility and extensive liver metabolism. The following study aimed to formulate specifically controlled release nano‐vehicles for oral and parenteral delivery of ZP to enhance its oral bioavailability and biological activity. A modified single emulsification–solvent evaporation method of sonication force was adopted to optimize the inclusion of ZP into biodegradable nanoparticles (NPs) using poly (dl‐lactic‐co‐glycolic acid) (PLGA). The impacts of various formulation variables on the physicochemical characteristics of the ZP‐PLGA‐NPs and drug release profiles were investigated. Pharmacokinetics and pharmacological activity of ZP‐PLGA‐NPs were studied using experimental animals and were compared with generic ZP tablets. Assessment of gamma‐aminobutyric acid (GABA) level in plasma after oral administration was conducted using enzyme‐linked immunosorbent assay. The maximal electroshock‐induced seizures model evaluated anticonvulsant activity after the parenteral administration of ZP‐loaded NPs. The prepared ZP‐PLGA NPs were negatively charged spherical particles with an average size of 120–300 nm. Optimized ZP‐PLGA NPs showed higher plasma GABA levels, longer sedative, hypnotic effects, and a 3.42‐fold augmentation in oral drug bioavailability in comparison to ZP‐marketed products. Moreover, parenteral administration of ZP‐NPs showed higher anticonvulsant activity compared to free drug. Oral administration of ZP‐PLGA NPs achieved a significant improvement in the drug bioavailability, and parenteral administration showed a pronounced anticonvulsant activity.
Polymeric nanoparticles (PNPs) have a great potential as drug delivery systems regarding their small size, high physicochemical stability, and sustainedrelease properties. Zaleplon (Za) is a model BCS class II drug with sedative and hypnotic actions. Zaleplon loaded polymeric nanoparticles (Za-NPs) were prepared from Eudragit ® RS100 using a single emulsion solvent evaporation technique. Full factorial design (2 3) was applied to optimize the physicochemical characterization of Za-NPs. The three independent variables were the amount of polymer, the concentration of PVA and the volume of organic phase. The effects of these variables on particle size (PS), zeta potential (ZP), entrapment efficiency (%EE) and in vitro drug release were investigated. In-vivo study was conducted in rats to evaluate the pharmacological effects of the selected Za-NPs formulations. The designed formulations of Za-NPs had a spherical shape with a size range of 146 to 250 nm and a positive zeta potential in the range of 17.7 to 39.3 mv. The % EE of Za-NPs formulations were in the range of 66.3 to 87.6%. Differential thermal analysis (DTA) showed no interaction between Zaleplon and other excipients meanwhile a change in drug crystallinity was observed. Za-NPs showed a significant increase in the sedative effects in vivo compared with the free drug. Stability studies of the selected lyophilized Za-NPs formulations indicated a high stability after 3 months.
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