Atorvastatin calcium (AC)-loaded nanoparticles (NPs) of mean particle diameter <100 nm and narrow distribution were prepared and characterized. Their in vivo PK as well as PD measures following oral administration in different dosage regimens in hyperlipidemic rats were evaluated. The results revealed that the oral bioavailability of two selected AC-NPs formulations was 235% and 169% relative to Lipitor. However, the treatment regimens were not superior in reducing serum total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) levels compared to Lipitor. Moreover, the AC-NPs treatments were associated with significant adverse effects observed biochemically and histologically. These results were contradictory with those obtained from a previous study in which similarly formulated AC-NPs of mean particle diameter >200 nm were found to be more safe and effective in reducing TC, LDL, and TG levels when administered to hyperlipiemic rats at reduced dosing frequency compared to daily dose of Lipitor despite their lower oral bioavailability. The discrepant correlation between pharmacokinetics (PK) and pharmacodynamics (PD) results was suggested to pertain to the different biodistribution profiles of AC-NPs depending on their sizes. Hereby, we provide a simple approach of particle size modulation to enhance the efficacy and safety of atorvastatin.

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With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

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