Effects of Rosuvastatin Versus Atorvastatin, Alone or in Combination, on Lipoprotein (a).

BACKGROUND: There are little evidences about the therapeutic efficacy of different lipid-lowering agents in the reduction of elevated lipoprotein(a) [Lp(a)]. OBJECTIVE: testing the effect of different lipid-lowering agents on elevated Lp(a). METHODS: prospective interventional study performed in patients with CAD, or high CAD risk, with Lp(a), >50 mg/dL. Lp(a), total cholesterol (C), HDL-C, LDL-C, triglycerides (TGs), apolipoprotein (Apo) A1, Apo B, enzymes of myocyte and hepatic injury were comparatively analyzed between 4 lipid-lowering strategies: rosuvastatin (R group) 40 mg, atorvastatin (A group) 80 mg, atorvastatin 40 mg add-on micronized fenofibrate (A+F group), and atorvastatin 40 mg add-on 1 g extended-release niacin (A+ERN group). Comparison was made for their therapeutic efficacy on Lp(a), and safety. RESULTS: 87 patients with mean Lp(a) 94.6 ± 39.6 mg/dL were analyzed. Groups: 25 patients in the R, 22 in the A, 20 in the A+F and 20 in A+ERN group. Significant reduction in all lipid fractions in all treatment groups was reported after 6 months. The average reduction of Lp(a) was 15.9 ± 21.0 mg/dL, with: 18.2 ± 24.8 (P = 0.001) in the R group, 17.3 ± 10.4 (P = 0.001) in A+F, 19.5 ± 10.9 (P = 0.001) in A+ERN and the lowest in the A group (11.24 ± 22.91, P = 0.032). No adverse effects were observed in any of the treatment groups. CONCLUSIONS: When compared with atorvastatin, it seems that rosuvastatin can achieve more significant decrease of Lp(a).The efficacy of the second one can be increased by adding fibrate or ERN.

Application of Design of Expert software for evaluating the influence of formulation variables on the encapsulation efficacy, drug content and particle size of PEO-PPO-PEO/Poly (DL-lactide-co-caprolactone) nanoparticles as carriers for SN-38.

Background and aims: Hydrophobic substances are mainly encapsulated into polymer nanocarriers in order to improve their solubility, enable their administration, at the same time to empower targeted tissue or cell specific delivery of the drug using the encapsulating vehicle as targeting and controlled release platform. 7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan, showing 100-fold to 1000-fold higher effect than Irinotecan, but its clinical use is limited because of its extreme hydrophobicity, as it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. Method: In order to fully exploit the potential of the nanoprecipitation as a method for preparation of Poly(DL-lactide-co-caprolactone)-poly(ethylene oxide) - poly(propylene oxide) - poly(ethylene oxide) (P(DL)LCL/PEO-PPO-PEO) nanoparticles and evaluate the influence of the polymer P(DL)LCL, stabilizing agent PEO-PPO-PEO copolymer (Lutrol F127) and the drug concentration (SN-38) upon drug entrapment efficiency, size and drug content, a D-optimal experimental design for response surface using Design Expert Version 9.0.4.1. software investigation was created and statistically analyzed. Results: We have observed that at higher SN-38 concentration during the preparation procedure (nanoprecipitation, solvent diffusion method), and due to its extremely low water solubility, the drug will start to precipitate as unprotected crystals at a faster pace compared to polymer aggregation, leading to extremely low encapsulation efficacy and waste of the active compound. The most desirable combination of factor settings are SN-38 = 0.5 mg, Polymer = 5 mg and F127 = 4%. Conclusion: This investigation utilizes the design of experiment approach and extends the primary understanding of impact of formulation development of P(DL)LCL/PEO-PPO-PEO nanoparticles as carriers for SN-38.

A review of the current understanding of nanoparticles protein corona composition.

Upon entering into the biological environments, the surface of the nanoparticles is immediately coated with proteins and form the so-called a protein corona due to which a nanoparticle changes its "synthetic" identity to a new "biological" identity. Different types of nanoparticles have different protein binding profiles, which is why they have different protein corona composition and therefore it cannot be said that there is a universal protein corona. The composition and amount of protein in the corona depends on the physical and chemical characteristics of the nanoparticles, the type of biological medium and the exposure time. Protein corona increases the diameter but also changes the composition of the surface of the nanoparticles and these changes affect biodistribution, efficacy, and toxicity of the nanoparticles.