Topical drug delivery is an attractive alternative to conventional methods because of advantages such as non-invasive delivery, by-pass of first pass metabolism, and improved patient compliance. However, several factors such as skin, physicochemical properties of the drug, and vehicle characteristics influence the permeation. Within a formulation, critical factors such as concentration of drug, physical state of drug in the formulation, and organoleptic properties affect the flux across the skin. The aim of the study was to develop and investigate topical semisolid preparations (creams and gels) with ibuprofen as the model drug and investigate the effect of various formulation parameters on the in-vitro performance across the Strat-M® membrane using flow-through cells. In addition, the physical stability of the developed formulations was investigated by studying viscosity, pH, and appearance. All the formulations developed in the study had appealing appearance with smooth texture and no signs of separation. Viscosity and pH of the formulations were acceptable. Cumulative amount of drug permeated at the end of 24 h was highest for clear gel (3% w/w ibuprofen; F6: 739.6 ± 36.1 µg/cm2) followed by cream with high concentration of ibuprofen in suspended form (5% w/w; F3: 320.8 ± 17.53 µg/cm2), emulgel (3% w/w ibuprofen; F5: 178.5 ± 34.5 µg/cm2), and cream with solubilized ibuprofen (3% w/w; F2A: 163.2 ± 9.36 µg/cm2). Results from this study showed that permeation of ibuprofen was significantly influenced by formulation parameters such as concentration of ibuprofen (3% vs. 5% w/w), physical state of ibuprofen (solubilized vs. suspended), formulation type (cream vs. gel), mucoadhesive agents, and viscosity (high vs. low). Thus, findings from this study indicate that pharmaceutical formulation scientists should explore these critical factors during the early development of any new topical drug product in order to meet pre-determined quality target product profile.

TY. Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine. Am J Physiol Endocrinol Metab 300: E848 -E857, 2011. First published February 8, 2011 doi:10.1152/ajpendo.00534.2010.-Ossabaw swine fed excess kilocalorie diet develop metabolic syndrome (MS) characterized by obesity, hypertension, insulin resistance, and glucose intolerance with/ without dyslipidemia. The purpose of this study was to test the hypothesis that MS would have a detrimental effect on skeletal muscle structure and cause changes in the expression of myosin heavy chains (MHCs). Adult male Ossabaw swine were fed for 24 wk highfructose or high-fat/cholesterol/fructose diets to induce normolipidemic MS (MetS) or dyslipidemic MS (DMetS), respectively, and were compared with the lean swine on control diet. MetS swine showed mild MS, lacking increases in total and low density lipoprotein (LDL) cholesterol, both of which were highly upregulated in DMetS swine. There was an ϳ1.2-fold increase in the cross-sectional areas of muscle fibers in MetS and DMetS groups compared with control for biceps femoris and plantaris muscles. In plantaris muscles, DMetS diet caused an ϳ2-fold decrease in slow MHC mRNA and protein expression and an ϳ1.2-to 1.8-fold increase in the number of intramyocellular lipid (IMCL) droplets without large changes in the size of the droplets. There was a trend to the decrease in slow MHC expression in muscles of swine on MetS diet. The number of IMCL droplets in muscle fibers of the MetS group was comparable to controls. These data correlate well with the data on total plasma cholesterol (control ϭ 60, MetS ϭ 70, and DMetS ϭ 298 mg/dl) and LDL (control ϭ 29, MetS ϭ 30, and DMetS ϭ 232 mg/dl). We conclude that structural changes observed in skeletal muscle of obese Ossabaw swine correlate with those previously reported for obese humans. obesity; fiber type composition; intramyocellular lipids; myosin heavy chains SKELETAL MUSCLE CONSTITUTES more than 40% of the total body weight and is one of the most important organs for glucose homeostasis. The mass and composition of skeletal muscle are critical for its functions. Obesity is a major risk factor for the development of both insulin resistance and noninsulin-dependent diabetes mellitus (NIDDM). Obesityrelated abnormalities lead to excessive accumulation of triglycerides and fatty acids in skeletal muscle fibers in the form of intramyocellular lipids (IMCL). IMCL accumulation is strongly associated with the impairment of glucose metabolism, oxidative stress, deficiency in energy production, insulin resistance, and eventually the development of type 2 diabetes (reviewed in Refs. 3 and 26).The fiber type composition of skeletal muscle has strong effects on metabolism and utilization of glucose and lipids. Lillioja et al. (22) showed that in vivo insulin action determined by the euglycemic clamp was positively correlated with the percentage of type 1 fibers and negatively correlated with the percentage of type 2b/x fibers in vastus lateralis ...

Cryoprotectants are often required in lyophilization to reduce or eliminate agglomeration of solute or suspended materials. The aim of this study was to select a cryoprotecting agent and optimize its concentration in a solid lipid nanoparticle formulation. Progesterone-loaded stearic acid solid lipid nanoparticles (SA-P SLNs) were prepared by hot homogenization with high speed mixing and sonication. The stearic acid content was 4.6% w/w and progesterone was 0.46% w/w of the initial formulation. Multiple surfactants were evaluated, and a lecithin and sodium taurocholate system was chosen. Three concentrations of surfactant were then evaluated, and a concentration of 2% w/w was chosen based on particle size, polydispersity, and zeta potential. Agglomeration of SA-P SLNs after lyophilization was observed as measured by increased particle size. Dextran, glycine, mannitol, polyvinylpyrrolidone (PVP), sorbitol, and trehalose were evaluated as cryoprotectants by both an initial freeze–thaw analysis and after lyophilization. Once selected as the cryoprotectant, trehalose was evaluated at 5%, 10%, 15%, and 20% for optimal concentration, with 20% trehalose being finally selected as the level of choice. Evaluation by DSC confirmed intimate interaction between stearic acid and progesterone in the SA-P SLNs, and polarized light microscopy shows successful lyophilization of the trehalose/SA-P SLN. A short term 28-day stability study suggests the need for refrigeration of the final lyophilized SA-P SLNs in moisture vapor impermeable packaging.

Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.

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