Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs.

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.

Injectable dual thermoreversible hydrogel for sustained intramuscular drug delivery.

Herein, we reported novel docetaxel-decorated solid lipid nanoparticle (DCT-SLN)-loaded dual thermoreversible system (DCT-DRTS) for intramuscular administration with reduced burst effect, sustained release and improved antitumor efficacy. The optimized DCT-DRTs was subjected to in-vitro and in-vivo analyses. Antitumor evaluation of the DCT-DRTS was executed and compared with DCT-hydrogel, and DCT-suspension trailed by the histopathological and immune-histochemical analyses. The DCT-SLN gave a mean particle size of 157 nm and entrapment efficiency of 93 %. It was a solid at room temperature, and changed to liquid at physiological temperature due to its melting point of about 32 °C. Unlikely, poloxamer mixture remained liquefied at 25-27 °C, however converted to gel at physiological temperature. This behavior demonstrated opposed reversible property of the DCT-SLN and poloxamer hydrogel in DCT-DRTS system, making it ideal for intramuscular administration and quick gelation inside the body. The DCT-DRTS sustained the drugs release and unlike DCT-hydrogel, the preliminary plasma concentration of DCT-DRTS was significantly reduced, overcoming the burst release. A meaningfully enhanced antitumor efficacy and improved survival rate was observed from DCT-DRTS in tumor cell xenograft athymic nude mice. Additionally, increased apoptotic and reduced proliferation markers were observed in DCT-DRTS treated tumor masses. It was concluded that DCT-DRTS may be a suitable choice for intramuscular administration of DCT with sustained release, improved bioavailability, reduced toxicity and enhanced antitumor effects.

Establishment of nanoparticle screening technique: A pivotal role of sodium carboxymethylcellulose in enhancing oral bioavailability of poorly water-soluble aceclofenac.

A novel nanoparticle screening technique was established to mostly enhance the aqueous solubility and oral bioavailability of aceclofenac using nanoparticle systems. Among the polymers investigated, sodium carboxymethylcellulose (Na-CMC) showed the greatest increase in drug solubility. Utilizing spray-drying technique, the solvent-evaporated solid dispersion (SESD), surface-attached solid dispersion (SASD), and solvent-wetted solid dispersion (SWSD) were prepared using aceclofenac and Na-CMC at a weight ratio of 1:1 in 50 % ethanol, distilled water, and ethanol, respectively. Using Na-CMC as a solid carrier, an aceclofenac-loaded liquid self-emulsifying drug delivery system was spray-dried and fluid-bed granulated together with microcrystalline cellulose, producing a solid self-nanoemulsifying drug delivery system (SNEDDS) and solid self-nanoemulsifying granule system (SNEGS), respectively. Their physicochemical properties and preclinical assessments in rats were performed. All nanoparticles exhibited very different properties, including morphology, crystallinity, and size. As a result, they significantly enhanced the solubility, dissolution, and oral bioavailability in the following order: SNEDDS ≥ SNEGS > SESD ≥ SASD ≥ SWSD. Based on our screening technique, the SNEDDS was selected as the optimal nanoparticle with the highest bioavailability of aceclofenac. Thus, our nanoparticle screening technique should be an excellent guideline for solubilization research to improve the solubility and bioavailability of many poorly water-soluble bioactive materials.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Novel rivaroxaban-loaded microsphere systems with different surface microstructure for enhanced oral bioavailability.

This study compares rivaroxaban-loaded polymeric microsphere systems with three types of surface microstructure. Three types of polymeric microspheres loaded with rivaroxaban were fabricated using a spray-drying technique: solvent-evaporated, surface-attached, and solvent-wet microspheres, depending on whether the drug and additives used are soluble in the solvent. The solvent-evaporated and surface-attached microspheres had a rivaroxaban/polyvinylpyrrolidone/sodium lauryl sulfate (SLS) weight ratio of 1/0.25/2.2, and the solvent-wetted microspheres contained rivaroxaban/polyvinyl alcohol/SLS in equal weight ratio (1/0.25/2). The physicochemical properties of the microspheres were evaluated using scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and particle size distribution analysis. The aqueous solubility and dissolution rate of rivaroxaban in the three types of microspheres were compared to those of the drug powder. The solvent-evaporated, surface-attached, and solvent-wetted microspheres were approximately 208, 140, and 172 times as soluble as the drug powder, and the final dissolution rate (120 min) was approximately 5, 2, and 4 times that of the drug powder, respectively. In addition, the oral bioavailability increased by approximately 2, 1.3, and 1.6 times compared to that of the drug powder (area under drug concentration-time curve: 2101.3 ± 314.8, 1325.2 ± 333.3, and 1664.0 ± 102.6 h·ng/mL, respectively). Finally, the solvent-evaporated microspheres showed the greatest improvement (solvent evaporating microspheres > solvent wetted microspheres > surface-attached microspheres ≥ drug powder). Therefore, the solvent-evaporated microspheres may represent a novel oral dosage form that improves the oral bioavailability of rivaroxaban, a poorly soluble drug.

Impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system and self nano-emulsifying granule system.

The purpose of this study was to investigate the impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system (SNEDDS) and self nano-emulsifying granule system (SEGS). The mesoporous calcium silicate (Ca-silicate) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) were utilised as hydrophobic carrier and hydrophilic carrier, respectively. The liquid SNEDDS formulation, composed of Tween80/Kollipohr EL/corn oil (35/50/15%) with 31% (w/w) dexibuprofen, was spray-dried and fluid-bed granulated together with Avicel using Ca-silicate or HP- ß-CD as a solid carrier, producing four different solid SNEDDS and SEGS formulations. Unlike the Ca-silicate-based systems, spherical shape and aggregated particles were shown in HP-ß-CD-based solid SNEDDS and SEGS, respectively. Molecular interaction was detected between Ca-silicate and the drug; though, none was shown between HP-ß-CD and the drug. Each system prepared with either carrier gave no significant differences in micromeritic properties, crystallinity, droplet morphology, size, dissolution and oral bioavailability in rats. However, the HP-ß-CD-based system more significantly improved the drug solubility than did the Ca-silicate-based system. Therefore, both carriers hardly affected the properties of both solid SNEDDS and SEGS; though, there were differences in the aspect of appearance, molecular interaction and solubility.

RNA Nanomedicine: Delivery Strategies and Applications.

Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges. In this review, we discuss different strategies employed in the design and development of nanomaterials for RNA delivery. We also highlight recent advances in the pharmaceutical applications of RNA delivered via nanomaterials. Various nanomaterials, such as lipids, polymers, peptides, nucleic acids, and inorganic nanomaterials, have been utilized for delivering functional RNAs, including messenger RNA (mRNA), small interfering RNA, single guide RNA, and microRNA. Furthermore, the utilization of nanomaterials has expanded the applications of functional RNA as active pharmaceutical ingredients. For instance, the delivery of antigen-encoding mRNA using nanomaterials enables the transient expression of vaccine antigens, leading to immunogenicity and prevention against infectious diseases. Additionally, nanomaterial-mediated RNA delivery has been investigated for engineering cells to express exogenous functional proteins. Nanomaterials have also been employed for co-delivering single guide RNA and mRNA to facilitate gene editing of genetic diseases. Apart from the progress made in RNA medicine, we discuss the current challenges and future directions in this field.

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol.

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.

Lysyl oxidase-responsive anchoring nanoparticles for modulation of the tumor immune microenvironment.

In the tumor microenvironment, lysyl oxidase (LOX) is known to play a key role in stabilizing the tumor extracellular matrix. Here, we designed LOX-responsive nanoparticles to interact with the collagen matrix of the tumor microenvironment. Collagen-coated and imiquimod-loaded polydopamine nanoparticles (CPN/IQ) could form crosslinked structures with the collagen matrix via LOX. In vitro, anchoring of CPN/IQ nanoparticles was observed with LOX-secreting CT26 cells, but this was blocked by a LOX inhibitor. In CT26 tumor-bearing mice, co-administration of nanoparticles plus the LOX inhibitor did not significantly alter the antitumor efficacy among nanoparticles. In the absence of the LOX inhibitor, however, a single administration of CPN/IQ could provide sustained responsiveness to near-infrared irradiation and ablation of primary tumors. In the primary tumor microenvironment, CPN/IQ lowered the Treg cell population but increased the cytotoxic CD3+CD8+ T cell population. In splenic dendritic cells, CPN/IQ treatment significantly increased the CD11c+CD86+ and CD11c+CD80+ cell populations. In a CT26 distant tumor-rechallenge model, CPN/IQ treatment increased the cytotoxic CD3+CD8+ T cell population and provided 100% survival of mice until 64 days. This study indicates the feasibility of tumor immune microenvironment modulation using LOX-responsive size-transforming nanoparticles. Although we tested the concept in a CT26 cell-derived tumor model, the concept of LOX-responsive collagen matrix- anchoring nanoparticles may be broadly applied to other tumor tissues with LOX-rich tumor microenvironments.

External cold atmospheric plasma-responsive on-site hydrogel for remodeling tumor immune microenvironment.

Although immunotherapy has recently emerged as a promising anti-tumor approach, it remains limited by the immunosuppressive tumor microenvironment. Cold atmospheric plasma irradiation can generate reactive oxygen species and trigger the presentation of tumor-associated antigens. Here, we exploited cold atmospheric plasma for on-site hydrogel application in the tumor environment, aiming to facilitate the sustainable uptake of tumor-associated antigens and nanoadjuvants by dendritic cells. Hyaluronic acid-tyramine conjugate was intratumorally injected as a liquid and formed an on-site hydrogel under irradiation with cold atmospheric plasma. Intratumoral delivery of hyaluronic acid-tyramine conjugate with transforming growth factor ß-blocking nanoadjuvant (TLN) followed by cold atmospheric plasma irradiation yielded a micro-network of TLN-loaded hydrogel (TLN@CHG). In vivo intratumoral injection of TLN@CHG promoted the activation of dendritic cells and more effectively increased the proportion of CD4 T cells and CD8 T cells in the tumor microenvironment, compared to the groups receiving TLN or hydrogel alone. Moreover, in CT26 tumor model mice, cold atmospheric plasma-induced TLN@CHG therapy ablated the primary tumor and provided 100% survival among mice rechallenged with CT26 cells. Taken together, our findings suggest that an on-site hydrogel-based micro-network of TLN has the potential to remodel the tumor immune microenvironment. Although we used TLN in this study, the concept could be extended to support the sustained action of other nanoadjuvants in a hydrogel micro-network.

Psychometric properties of the Barriers Self-Efficacy Scale for Physical Activity-Korean.

This study examined the psychometric properties of the Barriers Self-Efficacy Scale-Physical Activity for Korean-speaking adults with osteoarthritis at risk for metabolic syndrome (N = 150). Factor analysis identified three dimensions of the Korean Barriers scale, explaining 65.9 % of the total variance. Confirmatory factor analysis indicated that the structural validity adequately fits the data. Construct validity confirmed significant associations between the amount of physical activity and psychological variables. The test-retest reliability was 0.87; the alpha was 0.90. The standardized response mean (0.497) indicated responsiveness to medium-magnitude change. The Korean Barriers scale can assess self-efficacy to engage in regular physical activity in clinical settings.

Prediction of Fishman's skeletal maturity indicators using artificial intelligence.

The present study aimed to evaluate the performance of automated skeletal maturation assessment system for Fishman's skeletal maturity indicators (SMI) for the use in dental fields. Skeletal maturity is particularly important in orthodontics for the determination of treatment timing and method. SMI is widely used for this purpose, as it is less time-consuming and practical in clinical use compared to other methods. Thus, the existing automated skeletal age assessment system based on Greulich and Pyle and Tanner-Whitehouse3 methods was further developed to include SMI using artificial intelligence. This hybrid SMI-modified system consists of three major steps: (1) automated detection of region of interest; (2) automated evaluation of skeletal maturity of each region; and (3) SMI stage mapping. The primary validation was carried out using a dataset of 2593 hand-wrist radiographs, and the SMI mapping algorithm was adjusted accordingly. The performance of the final system was evaluated on a test dataset of 711 hand-wrist radiographs from a different institution. The system achieved a prediction accuracy of 0.772 and mean absolute error and root mean square error of 0.27 and 0.604, respectively, indicating a clinically reliable performance. Thus, it can be used to improve clinical efficiency and reproducibility of SMI prediction.

Hinged Roof Reconstruction of Anterior Iliac Crest after Harvesting Bicortical Strut Graft for Anterior Cervical Fusion.

Introduction: The strut iliac bone graft has been widely used to achieve fusion in various anterior cervical spinal surgeries but some complications often remain, such as pain and gross deformity. Considering these, we designed a new technique to restore the iliac ridge, using the outmost part of the iliac crest. We aim to assess the efficacy of our new restoration technique of the iliac ridge after harvesting strut bone graft for anterior cervical fusion. The clinical and radiological outcomes of our hinged roof method were evaluated. Technical Note: A retrospective review was conducted of 29 patients who underwent hinged roof reconstruction of the iliac ridge after harvesting a bicortical strut bone graft for anterior cervical fusion using a cervical plate system. The clinical outcome for pain and gross appearance and radiological results were evaluated. Three months after the surgery, pain at the donor site became minimal or absent in all cases. At 1 year follow-up, no patient had reported pain and palpable discomfort, such as step-off on the donor site. Final X-ray and follow-up computed tomography revealed a bony union of the reconstructed iliac ridge to both margins. Conclusions: By showing good clinical and radiological outcomes, the authors' hinged roof reconstruction of the iliac crest after harvesting strut bone graft seemed to be a simple and effective technique that can reduce complications, such as pain and deformity on the donor iliac crest.

Skin irritation in children undergoing orthodontic facemask therapy.

Orthodontic facemasks are extraoral orthodontic appliances that influence maxillary and mandibular development in children with skeletal Class III malocclusion. While a facemask is most effective in patients before the growth spurt, skin irritation is common during the treatment. Therefore, this retrospective study aimed to investigate the prevalence and pattern of such skin changes and identify their possible associated risk factors. We included 177 patients with skeletal Class III malocclusion who underwent facemask therapy. Patient age and sex, orthodontic parameters expressing the severity of malocclusion, the presence of complaints in the temporomandibular joint (TMJ) areas, and the level of patient cooperation were evaluated. Additionally, the severity and onset time of skin reactions were further analyzed. The results indicated that 43.5% of patients developed skin changes typical of irritant contact dermatitis. Skin irritation was significantly associated with the presence of TMJ complaints and female sex. Furthermore, skin irritation was more common in younger patients. Clinicians should pay special attention to the skin areas that come into contact with the appliance during each follow-up visit to detect potential problems. Moreover, patients and their parents should be given adequate information about the possibility, prevention, and management of skin problems during facemask therapy.

Development of guar gum-based dual-layer wound dressing containing Lactobacillus plantarum: Rapid recovery and mechanically flexibility.

This study aimed to develop a Lactobacillus plantarum (L. plantarum)-loaded dual-layer wound dressing (DLD) with excellent wound recovery and mechanical properties. L. plantarum-loaded DLD was fabricated by covering the hydrogel (inner layer) with a hydrocolloid (external layer). The hydrocolloid was manufactured by the hot-melt method, consisting of liquid paraffin, polyisobutylene, styrene-isoprene-styrene, and sodium carboxymethylcellulose (12:20:25:43, w/w/w/w). In contrast, the hydrogel was fabricated by the freeze-and-thaw method to load heat-labile L. plantarum. Various non-ionic materials have been investigated to select appropriate hydrogel components. The hydrogel composed of L. plantarum stock solution, guar gum, and polyvinyl alcohol (10:2:10, w/w/w) was chosen for its excellent swelling capacity and mechanical properties. As a result, heat-labile L. plantarum was successfully loaded into the guar-gum-based DLD. Moreover, guar gum-based DLD containing L. plantarum exhibited significantly enhanced swelling capacity and elasticity compared to single hydrogel layer (swelling capacity: DLD, 920.7 ± 32.4 % vs. hydrogel, 282.2 ± 6.5 %; elastic modulus: DLD, 2.9 ± 0.3 × 10-3 N/mm2 vs. hydrogel, 4.2. ± 0.7 × 10-3 N/mm2). The wound recovery test using Pseudomonas aeruginosa-infected animal model and histological profiles confirmed guar gum-based DLD containing L. plantarum to elicit accelerated wound recovery with complete re-epithelialization compared to commercial product and non-treated (recovery rate at Day 3: DLD, 67.8 ± 6.2 % vs. commercial product, 30.4 ± 11.7 % vs. non-treated, 14.2 ± 7.5 %). Therefore, L. plantarum-loaded DLD is an effective system for wound treatment.

Influence of hydrophilic polymers on mechanical property and wound recovery of hybrid bilayer wound dressing system for delivering thermally unstable probiotic.

In this study, a novel hybrid bilayer wound dressing (HBD) has been developed for delivering a thermally unstable probiotic, Lactobacillus brevis. The HBD was composed of two layer, a hydrocolloid layer and a Lactobacillus brevis-loaded hydrogel layer as a block supporter and drug carrier, respectively. Moreover, various probiotic-loaded hydrogel layers in HBD were prepared with polyvinyl alcohol (PVA) and numerous hydrophilic polymers via a freezing and thawing method, and their mechanical property, release and wound recovery were assessed. Among the hydrophilic polymers investigated, copovidone most improved the mechanical strength, swelling ability, and release properties; and thus, copovidone/PVA (ratio of 1.0/10) was determined as an appropriate composition of hydrogel layer in HBD. The selected HBD exhibited superior stability than conventional dressing, maintaining approximately 90% of Lactobacillus brevis (9.0 × 108 CFU) during the preparation and storage process. Moreover, the HBD had about 5- and 4-fold better swelling ability and elasticity compared to the conventional dressing. Additionally, it exhibited superior recovery efficacy than the commercial dressing in the animal study. Therefore, this HBD system for delivering a thermally unstable Lactobacillus brevis would be a promising wound dressing with excellent mechanical property and wound recovery.

Psychometric Properties of the Korean Version of the Patient Knowledge Questionnaire-Osteoarthritis.

This study examined the psychometric properties of the Korean version of the Patient Knowledge Questionnaire-Osteoarthritis (PKQ-OA-K). A cross-sectional survey was conducted with 157 adults with osteoarthritis from the outpatient clinic at a university hospital in Korea. The overall correct answer rate for the PKQ-OA-K was 60.4%; notably, the drug therapy subscale had the lowest median score percentage (42.9%). For structural validity, exploratory factor analysis identified the PKQ-OA-K as two-dimensional, explaining 52.4% of the total variance. Confirmatory factor analysis showed that the two-factor model adequately fit the data. The PKQ-OA-K was positively correlated with education level (r = 0.24) and osteoarthritis outcomes (r = 0.17), thus verifying the hypotheses of construct validity. The intraclass correlation coefficient for test-retest reliability was 0.52; alpha was 0.44. The PKQ-OA-K has excellent validity but imperfect reliability for adults with osteoarthritis. This study recommends cautious use of the PKQ-OA-K to assess Korean patients' knowledge of osteoarthritis.

Correlation and Correspondence between Skeletal Maturation Indicators in Hand-Wrist and Cervical Vertebra Analyses and Skeletal Maturity Score in Korean Adolescents.

This retrospective observational study aimed to examine the correlation and correspondence between skeletal maturation indicators (SMI), cervical vertebral maturation indicators (CVMI), and radius-ulna-short bones (RUS) skeletal maturity scores in Korean adolescents, and to determine whether easily obtainable SMI or CVMI can replace the RUS skeletal maturity score. A total of 1017 participants were included with both hand-wrist radiograph and lateral cephalogram acquired concurrently. From the lateral cephalogram, CVMI was determined; through the hand-wrist radiograph, SMI was categorized, and the RUS skeletal maturity score was evaluated as well. Associations were examined using the Mann-Whitney U test, Spearman's rank-order correlation analysis, and multiple correspondence analysis. There was no statistically significant difference in chronological age between males and females; however, the SMI, CVMI, and RUS skeletal maturity scores were significantly higher in females. The SMI, CVMI, and RUS skeletal maturity scores showed a statistically significant strong degree of both positive correlation and correspondence. However, a precisely corresponding RUS skeletal maturity score was difficult to obtain for a specific CVMI and SMI stage, implying the absence of a quantitative correlation. In conclusion, detailed evaluation should be conducted using the RUS skeletal maturity score, preferably in cases that require bone age determination or residual growth estimation.

Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres.

BACKGROUND: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared. METHODS: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier. RESULTS: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL). CONCLUSION: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.

Gender Difference in the Relationship Between Pulse Pressure and Visceral Adiposity Index in Korean Adults.

Background: This study was conducted to assess the association of pulse pressure (PP) and visceral adiposity index (VAI) by gender in Korean adults. Methods: This study used the data of 4960 adults at age ≥20 years, from the 2015 Korean National Health and Nutrition Examination Survey. Results: In the overall population (n = 4960), after adjustment for related variables and with quartile 1 of VAI as a reference, the odds ratios of high PP (PP >60 mmHg) was significantly higher in quartile 3 [1.32 (95% confidence interval [CI], 1.02-1.71)] and quartile 4 of VAI [1.40 (95% CI, 1.07-1.83)]. In women (n = 2784), the OR of high PP, with quartile 1 of VAI as a reference, was significantly higher in quartile 3 [2.36 (95% CI, 1.55-3.61)] and quartile 4 of VAI [2.70 (95% CI, 1.77-4.12)]. In men (n = 2176), high PP was not associated with the quartiles of VAI. In addition, after adjustment for related variables, the PP level was positively associated with the quartiles of VAI in the overall population (P < 0.001) and women (P < 0.001), but not in men (P = 0.316). Conclusions: VAI was positively associated with PP in Korean women, but not in Korean men.