Preparation and evaluation of polymeric microparticulates for improving cellular uptake of gemcitabine

Ji-Ho Lim1,*, Sung-Kyun You1,*, Jong-Suep Baek1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea, 2College of Pharmacy, Chonnam National University, Buggu, Gwangju, South Korea *These authors contributed equally to this workBackground: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects.Methods: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated.Results: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone.Conclusion: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.Keywords: gemcitabine, polymeric microparticulates, mucoadhesive, enteric coating, cellular uptake, oral absorptio

Change in the height of Korean children and adolescents: analysis from the Korea National Health and Nutrition Survey II and V

PurposeThe mean adult height of Koreans has increased since nationwide anthropological measurements began in 1967. The objective of this study was to evaluate differences in heights of Korean late adolescents and young adults within and between the Second and Fifth Korea National Health and Nutrition Examination Surveys (KNHANES II and V).MethodsKoreans aged ≤22 years with available measurements of height were enrolled from the KNHANES surveys (KNHANES II: n=3,372 [1,732 males and 1,640 females]; KNHANES V: n=6,190 [3,198 males and 2,992 females]). Differences in the height of KNHANES respondents within and between surveys were evaluated according to age and sex.ResultsIn KNHANES II, there was no significant difference in height between males aged 17-19 years and those aged 20-22 years (174.3±0.5 cm vs. 174.3±0.6 cm, P=0.995). Females aged 20-22 years were taller than those aged 17-19 years (159.8±0.4 cm vs. 161.0±0.4 cm, P=0.017). Females aged 17-19 years were significantly taller in KNHANES V than in KNHANES II (161.2±0.3 cm vs. 159.8±0.4 cm, P=0.004). Respondents aged 20-22 years were taller in KNHANES V than in KNHANES II, although not significantly so; the difference was 0.3±0.8 cm in males (P=0.721) and 0.5±0.6 cm in females (P=0.386).ConclusionKoreans appear to continue growing even in their late adolescence and early twenties. Consequently, it may be necessary to expand the reference age ranges of the Korean growth chart. Additionally, a longitudinal growth survey is needed to determine growth patterns and secular trend in height among Koreans

Sustained Cytotoxicity of Wogonin on Breast Cancer Cells by Encapsulation in Solid Lipid Nanoparticles

While wogonin has been known to have cytotoxicity against various cancer cells, its bioavailability and cytotoxicity are low due to its low water solubility. Therefore, wogonin-loaded solid lipid nanoparticles were fabricated using a hot-melted evaporation technique. The highest solubility of wogonin was observed in stearic acid. Hence, wogonin-loaded solid lipid nanoparticles were composed of stearic acid as the lipid matrix. The physicochemical properties of the wogonin-loaded solid lipid nanoparticles were evaluated by dynamic laser scattering and scanning electron microscopy. The wogonin-loaded solid lipid nanoparticles exhibited sustained and controlled release up to 72 h. In addition, it was observed that the wogonin-loaded solid lipid nanoparticles exhibited enhanced cytotoxicity and inhibited poly (ADP-ribose) polymerase in MCF-7 breast cancer cells. Overall, the results indicate that wogonin-loaded solid lipid nanoparticles could be an efficient delivery system for the treatment of breast cancer

Development and Evaluation of Tannic Acid-Coated Nanosuspension for Enhancing Oral Bioavailability of Curcumin

Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR

The Effect of Pharmaceutical Excipients for Applying to Spray-Dried Omega-3 Powder

Omega-3 fatty acid plays a role in protecting cells in the human body, maintaining the structure of the cell, and helping smooth metabolism. Also, it inhibits the formation of blood clotting and is effective in enhancing the formation of bone. However, the instability due to fatty acid oxidation and a fishy smell are the reasons it is avoided by people. In this study, we tried to obtain the omega-3 powder through spray-drying method using a variety of binders and surfactants for improving the limit of omega-3 fatty acid. First of all, an olive oil was used instead of omega-3 for optimization of the preparation of spray-dried omega-3 powder. Through the screening of binders and surfactants, γ-cyclodextrin and hydrogenated lecithin were chosen as a binder and a surfactant, respectively. Omega-3-loaded spray-dried powder was obtained, eventually. The morphology of omega-3-loaded spray-dried powder was spherical of 310 nm and the DHA amount was 98%. This study suggested that the transformation of omega-3 fatty acid into solid state by spray-drying using a binder and a surfactant was successively performed

The Improvement of Skin Whitening of Phenylethyl Resorcinol by Nanostructured Lipid Carriers

Phenylethyl resorcinol (4-(1-phenylethyl)1,3-benzenediol) (PR) is a new whitening agent that has been found to have the ability to inhibit tyrosinase activity. However, the application of PR is limited by photo instability and poor solubility. PR-loaded nanostructured lipid carriers (PR-NLCs) were prepared by the hot-melted ultrasonic method. Glycerol monostearate and olive oil were selected as the solid lipid and liquid lipid for considering the solubility of PR in liquid lipid and partition coefficient of PR in solid lipid, respectively. The particle size and polydispersity index of PR-NLCs were 57.9 ± 1.3 nm and 0.24 ± 0.01, respectively. The encapsulation efficiency and loading capacity of PR-NLCs were 93.1 ± 4.2% and 8.5 ± 0.4%, respectively. The stability test demonstrated that the incorporation of PR into NLCs conferred excellent physicochemical stability and photo stability for at least three months at 4 °C in the dark and 25 °C under daylight. In vitro release of PR-NLCs revealed a sustained release pattern. Cellular tyrosinase assay showed that PR-NLCs could significantly inhibit tyrosinase activity in melanoma cells, suggesting that NLCs can be used as a biocompatible nanocarrier for the effective delivery of skin whitening agents

Optimization of Mesoporous Silica Nanoparticles through Statistical Design of Experiment and the Application for the Anticancer Drug

The synthesis process or composition of mesoporous silica nanoparticles (MSNs) affects the physicochemical properties. Using these properties, MSNs were synthesized through the Box–Behnken design (BBD) among statistical experimental methods. The effect of the amounts of synthetic reagents, hexadecyl triethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), and 2 N sodium hydroxide (NaOH), was studied using the reaction surface design. Surface area, particle size, and zeta potential were set as response values. The physicochemical properties of the optimized MSNs were evaluated, and the effect as a drug delivery system was evaluated by loading doxorubicin hydrochloride (DOX). Nano-sized MSNs were successfully prepared with 0.617 g of CTAB, 8.417 mL of TEOS, and 2.726 mL of 2 N NaOH and showed excellent physicochemical properties. The optimized MSNs showed negligible toxicity in MCF-7 cells. The drug release profile from DOX-loaded MSNs (MSN@DOX) showed an increased rate of release with decreasing pH of the medium, with the release profile sustained for 48 h. In the cytotoxicity test, the sustained drug release mechanism of MSN@DOX was confirmed. This study proposed a new statistical approach to the synthesis of MSNs

The Correlation of Endoscopic Findings and Clinical Features in Korean Patients with Scrub Typhus: A Cohort Study.

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi-induced systemic vasculitis, but the involvement of the gastrointestinal tract and the endoscopic findings associated with scrub typhus are not well understood. We performed a prospective study and recommend performing esophagogastroduodenoscopy (EGD) for all possible scrub typhus patients, regardless of gastrointestinal symptoms. Gastrointestinal symptoms, endoscopic findings and clinical severity based on organ involvement and ICU admission were analyzed. Gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients. The major endoscopic findings were ulcers (43/127, 33.9%). Interestingly, 7.1% (9/127) of the patients presented with esophageal candidiasis. There was no correlation between the presence or absence of gastrointestinal symptoms and the endoscopic grade (P = 0.995). However, there was a positive correlation between the clinical severity and the endoscopic findings (P = 0.001). Sixty-three percent of the patients presented with erosion or ulcers on prospectively performed endoscopic evaluations, irrespective of gastrointestinal symptoms. Gastrointestinal symptoms did not reflect the need for endoscopy. Scrub typhus patients could have significant endoscopic abnormalities even in the absence of gastrointestinal symptoms