Bong Kyu Yoo

Evaluation of the effect of tacrolimus-loaded liquid crystalline nanoparticles on psoriasis-like skin inflammation.

Psoriasis is a chronic relapsing inflammatory skin disorder affecting 2–3% of world population. In present context, a novel topical formulation that could effectively deliver tacrolimus for psoriasis treatment would be of great interest. Liquid crystalline nanoparticle (LCN) is one of the potential drug delivery systems for topical drug delivery. Herein, the effects of tacrolimus-loaded LCNs on in vitro skin permeation and retention as well as on in vivo psoriasis-like skin inflammation are studied. Characterization of nanoparticles included particle size and entrapment efficiency analysis that presented nanoparticles of 149.1 nm for monoolein-based and 204.3 nm for oleic acid added monoolein-based nanoparticles with entrapment efficiency of tacrolimus above 99%. Skin permeation and retention study has revealed a significant increase in the amount of tacrolimus permeated and retained by the use of LCNs. Tacrolimus-loaded LCNs are more effective in the treatment of psoriasis-like skin inflammation as compared to tacrolimus dissolved in propylene glycol. Hence, this study provides a basis for possible applicability of tacrolimus-loaded LCNs in the treatment of psoriasis.

Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function.

To develop and optimize the novel self‐microemulsifying drug delivery system (SMEDDS) formulation for enhanced water solubility and bioavailability of telmisartan (TMS) using the Box–Behnken design (BBD) and desirability function.

Meta-analysis of the Efficacy and Safety of Secukinumab for the Treatment of Plaque Psoriasis

Background: In January 2015, US FDA approved secukinumab, a human interleukin-17A (IL-17A) antagonist, for the treatment of plaque psoriasis. Objective: To provide unbiased drug information about the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis by performing meta-analysis. Methods: PubMed and EMBASE database searches were conducted. Among the literatures retrieved, relevant Phase III clinical trials were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal and three non-pivotal Phase III clinical trials were retrieved. All the trials evaluated the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis with two co-primary endpoints: proportions of Psoriasis Area and Severity Index (PASI) responders and Investigator’s Global Assessment (IGA) responders. The overall odd ratios for proportions of PASI responders and IGA responders in secukinumab-containing arm were 65.6 and 62.5 compared to the placebo arm, respectively. Secukinumab was superior to etanercept resulting in both of the odd ratios being 3.7 compared to the etanercept. Secukinumab was generally well tolerated during the one year trial. However, as with other monoclonal antibody medications, vulnerability of respiratory infection (especially nasopharyngitis) was reported as most common adverse event. Conclusions: Meta-analysis of the seven Phase III clinical trials resulted in superiority of secukinumab over etanercept in terms of the efficacy and safety. However, long-term safety data is lacking at this time so post-marketing surveillance should be performed for any adverse events associated with the use of this new biological medication.

Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells.

In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds.

Effect of saturated fatty acids on tacrolimus-loaded liquid crystalline nanoparticles

Liquid crystalline nanoparticles are unique structures that can be used in the delivery of a wide range of pharmaceutical actives. Herein, we studied the effect of saturated fatty acids on tacrolimus-loaded monoolein liquid crystalline nanoparticles stabilized with poloxamer 407. Characterization of nanoparticles included optical and transmission electron microscopy, particle size, and entrapment efficiency analysis. Microscope data suggested the formation of cubosomes for monoolein dispersions, and of hexosomes for monoolein-fatty acid systems. Entrapment efficiency of tacrolimus was as high as 99 % or above. In vitro release study revealed that amount of monoolein and carbon chain lengths of the fatty acid were the factors that affected drug release from the liquid crystalline nanoparticles. Notably, monoolein-fatty acid systems prepared with short chain length, such as lauric and myristic acid, showed markedly sustained release profile of the drug. Hence, appropriate selection of fatty acid can be exploited to achieve desired release profile from monooloein liquid crystalline nanoparticles.

Skin permeation and retention of topical bead formulation containing tranexamic acid

The objective of this study is to develop a topical bead formulation of tranexamic acid (TA) which can be used concomitantly with laser treatment. The bead formulation of TA (TAB) was successfully prepared by fluidized bed drying method. Physicochemical properties of the TAB were evaluated in terms of chemical stability of TA and differential scanning calorimetry. TA in the bead was stable up to six months at 25°C and existed as amorphous state. In vitro skin permeation and in vivo skin retention of TA in the beads were significantly higher compared to a commercial product. When the bead was dissolved into distilled water and applied concomitantly with laser treatment, the amount of TA retained in the skin in the in vivo study was inversely proportional to the energy levels of laser treatment, indicating absorption into subcutaneous tissue and drainage to systemic circulation. Therefore, when laser treatment is used concomitantly with TAB, energy level should be very carefully monitored to avoid possible adverse events associated with systemic side effects of TA.