[Prevalence and risk factors of hyperuricemia among freshmen at Beijing Sport University from 2021 to 2022].

OBJECTIVE: To investigate the prevalence of hyperuricemia among freshmen enrolled in Beijing Sport University and to explore the influencing factors of hyperuricemia in the college population. METHODS: The study period was from September 2021 to February 2022.3372 freshmen of the class of 2021 from Beijing Sport University in Beijing were selected as the study subjects, and two blood uric acid tests were performed on non-same days to calculate the prevalence of the population and to explore the risk factors of hyperuricemia in the college student population using a case-control method.246 people were selected from the hyperuricemia patients of the population to be included in the case group by convenience sampling, and 211 people were selected from the non-hyperuricemia persons of the population to be included in the control group. They were included in the control group, underwent physical and laboratory examinations, and were retrospectively surveyed with questionnaires that included general information such as age, gender, specialty, place of birth, and diet related to hyperuricemia, awareness of hyperuricemia disease, physical activity level, and sleep. Statistical analysis was performed using chi-square analysis, one-way Logistic regression analysis, and multi-factor logistic regression analysis. RESULTS: The number of patients actually diagnosed with hyperuricemia by two blood uric acid tests on non-same days was 479, with a population prevalence rate of 14.21%. Among them, the number of males in the diseased population was 391(22.39%), and the number of females in the diseased population was 88(5.41%). A total of 457 subjects were enrolled in the case-control study, among them, 246 in the case group(218 males and 28 females, average age 19.74 years), 211 in the control group(177 males and 34 females, average age 19.93 years), and 247 in the case group, 211 in the control group, and 2 groups of subjects were included. A total of 211 subjects, and there was no significant difference between the 2 groups in terms of gender composition and age distribution. One-way logistic regression analysis showed that central obesity(OR=31.52, 95%CI 7.59-130.86), obesity(OR=2.59, 95%CI 1.20-5.58), overweight(OR=1.67, 95%CI 1.08-2.59), frequent consumption of fresh vegetables(OR=0.66, 95%CI 0.43-0.99), and drinking 1500-2000 mL of water per day(OR=0.63, 95%CI 0.41-0.95) were associated with hyperuricemia, and multifactorial Logistic regression analyses were performed to analyze the above factors, and finally central obesity(OR=32.05, 95%CI 7.65-134.20), BMI obesity(OR=3.22, 95%CI 1.44-7.20), and daily water intake of 1500-2000 mL(OR=0.60, 95%CI 0.37-0.95) were included in the model at the level of P=0.05. CONCLUSION: The current high prevalence of hyperuricemia in the college student population, which is more prevalent in male college students. Obesity and central obesity are risk factors for hyperuricemia in young college students, and daily water intake of 1500-2000 mL is a protective factor.

Preparation of High-Drug-Loaded Clarithromycin Gastric-Floating Sustained-Release Tablets Using 3D Printing.

The high-drug-loaded sustained-release gastric-floating clarithromycin (CAM) tablets were proposed and manufactured via semisolid extrusion (SSE)-based 3D printing. The physical and mechanical properties, such as dimensions, weight variation, friability, and hardness, were accessed according to the quality standards of Chinese Pharmacopoeia (Ch.P). The interactions among the drug-excipients were evaluated via differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) techniques. Next, the rheological properties of the paste and the effect of the excipients and solvents were evaluated. Finally, a very high drug-loading of up to 81.7% (w/w) with the sustain release time of 8 h (125 mg) and 12 h (250 mg) was achieved. The results revealed the potential of SSE for achieving a high drug loading and identified the suitable properties of the paste for SSE-based 3D printing.

Semi-solid extrusion 3D printing ODFs: an individual drug delivery system for small scale pharmacy.

Orodispersible films (ODFs) are promising drug delivery systems for customized medicines as it provide an alternative approach to increase consumer acceptance by advantages of rapid dissolution and administration without water. The aim of this study was to develop a platform to support the realization of tailored treatments suitable for the extemporaneous production of ODFs by semi-solid extrusion (SSE) 3D printing (3DP). Hydroxypropyl methyl cellulose (HPMC) was used as the polymer of ODFs, and levocetirizine hydrochloride was used as the model drug. The optimal formulation was HPMC:API:PS:maltitol:sucralose at a ratio of 64:10:10:15:1. Seventeen percent HPMC solution and optimal formulation were used to prepare film precursors. The impact of dynamic viscosities and fluid mechanics difference on printing applicability was discussed. The ODFs of cube designs with aimed dose of 1.25 mg, 2.5 mg, and 5 mg were printed by SSE 3DP. Good linear relationship between theoretical model volume and drug content (R2 = 0.999) and good dose accuracy indicate that 3DP is a suitable method for preparing individualized ODFs.

Applications of excipients in the field of 3D printed pharmaceuticals.

The aim of this study was to determine the effect of varying excipient content on the formation and physical properties of 3 D printed tablets. Fifteen different excipient preparations were formed into tablets with radii of 5 mm and thickness of 2 mm, using binder jetting (BJ). The tablets were analyzed by assessing visual and microstructural appearance, friability, hardness, and disintegration time. We found that filling agents with high water solubility (e.g. D-sucrose), binding agents with a high viscosity in solution (e.g. polyethylene glycol 4000) and moistening agent with higher water content can increase the bonding strength and hardness of the 3 D printed tablets and prolonged their disintegration time. This work has demonstrated that the type of excipient and its concentration affects the properties of the 3 D printed tablet. This article may be used as a guide for elucidation of the effects of using conventional tablet excipients in the field of 3 D printed pharmaceuticals. The present work should enable the identification of excipients that satisfy requirements, reduce analysis time, and improve efficiency.

Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells.

Three iridium(III) complexes ([Ir(Hppy)2(L)](PF6) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), 1; 5-nitro-6-amino-phenanthroline (NAP), 2; and 5,6-diamino-phenanthroline (DAP) 3 were synthesized and characterized. The cytotoxicities of Ir(III) complexes 1-3 against cancer cell lines SGC-7901, A549, HeLa, Eca-109, HepG2, BEL-7402, and normal NIH 3T3 cells were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) method. The results showed that the three iridium(III) complexes had moderate in vitro anti-tumor activity toward SGC-7901 cells with IC50 values of 3.6 ± 0.1 µM for 1, 14.1 ± 0.5 µM for 2, and 11.1 ± 1.3 µM for 3. Further studies showed that 1-3 induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca2+, high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes 1-3 can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that 1-3 induce apoptosis in SGC-7901 cells through ROS-mediated mitochondrial damage and DNA damage pathways, as well as by inhibiting cell invasion, thereby exerting anti-tumor cell proliferation activity in vitro.

A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone.

Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.

Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing.

Individualized medicine is a new direction in the field of modern pharmacy. In this study, we assessed the feasibility and accuracy of 3D printing techniques for the preparation of individualized doses of mouth-disintegrating tablets of warfarin. Warfarin sodium, D-sucrose, pregelatinized starch, povidone K30, microcrystalline cellulose, and silicon dioxide (at a ratio of 1:42.45:46.15:5.1:4.9:0.4) were mixed and used as the printing powder in the 3D printer; preset parameters were used. The dosage of the tablet was controlled by the number of printing layers. The content, dose uniformity, dose accuracy, hardness, friability, disintegration time, dissolution, and the microstructural and overall appearance were determined to evaluate the printed tablets. For the doses of 3, 2, and 1 mg that were produced in the experiment, the disintegration times were 50.0 ± 5.2, 35.7 ± 4.3, and 11.0 ± 2.2 s, respectively, and the relative errors of the dose were -2.33, -1.50, and 0%, respectively. The other indicators were consistent with the preparation requirements of pharmaceutical tablets. It is possible to prepare tablets with excellent properties and controlled drug doses by using 3D printing techniques. This technology will be an important means to achieve individualized medicine.

Molecular insights into sarcopenia: ferroptosis-related genes as diagnostic and therapeutic targets.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, leads to cell death. Growing evidence suggests the involvement of ferroptosis in sarcopenia. However, the fundamental ferroptosis-related genes (FRGs) for sarcopenia diagnosis, prognosis, and therapy remain elusive. This study aimed to identify molecular biomarkers of ferroptosis in sarcopenia patients. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal and sarcopenia samples were identified using the 'limma' package in R software. FRGs were extracted from GeneCards and FerrDB databases. Functional enrichment analysis determined the roles of DEGs using the 'clusterProfiler' package. A protein-protein network was constructed using Cytoscape software. Immune infiltration analysis and receiver operating characteristic (ROC) analysis were performed. mRNA-miRNA, mRNA-TF, and mRNA-drug interactions were predicted using ENCORI, hTFtarget, and CHIPBase databases. The network was visualized using Cytoscape. We identified 46 FRGs in sarcopenia. Functional enrichment analysis revealed their involvement in critical biological processes, including responses to steroid hormones and glucocorticoids. KEGG enrichment analysis implicated pathways such as carbon metabolism, ferroptosis, and glyoxylate in sarcopenia. Totally, 11 hub genes were identified, and ROC analysis demonstrated their potential as sensitive and specific markers for sarcopenia in both datasets. Additionally, differences in immune cell infiltration were observed between normal and sarcopenia samples. The hub genes identified in this study are closely associated with ferroptosis in sarcopenia and can effectively differentiate sarcopenia from controls. CDKN1A, CS, DLD, FOXO1, HSPB1, LDHA, MDH2, and YWHAZ show high sensitivity and specificity for sarcopenia diagnosis.Communicated by Ramaswamy H. Sarma.

Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1.

Rationale: The response rate to the MEK inhibitor trametinib in BRAF-mutated melanoma patients is less than 30%, and drug resistance develops rapidly, but the mechanism is still unclear. Yes1-associated transcriptional regulator (YAP1) is highly expressed in melanoma and may be related to MEK inhibitor resistance. The purpose of this study was to investigate the mechanism of YAP1 in MEK inhibitor resistance in melanoma and to screen YAP1 inhibitors to further determine whether YAP1 inhibition reverses MEK inhibitor resistance. Methods: On the one hand, we analyzed paired melanoma and adjacent tissue samples using RNA-seq and found that the Hippo-YAP1 signaling pathway was the top upregulated pathway. On the other hand, we evaluated the transcriptomes of melanoma samples from patients before and after trametinib treatment and investigated the correlation between YAP1 expression and trametinib resistance. Then, we screened for inhibitors that repress YAP1 expression and investigated the mechanisms. Finally, we investigated the antitumor effect of YAP1 inhibition combined with MEK inhibition both in vitro and in vivo. Results: We found that YAP1 expression levels upon trametinib treatment in melanoma patients were correlated with resistance to trametinib. YAP1 was translocated into the nucleus after trametinib treatment in melanoma cells, which could render resistance to MEK inhibition. Thus, we screened for inhibitors that repress YAP1 expression and identified multiple bromodomain and extra-terminal (BET) inhibitors, including NHWD-870, as hits. BET inhibition repressed YAP1 expression by decreasing BRD4 binding to the YAP1 promoter. Consistently, YAP1 overexpression was sufficient to reverse the proliferation defect caused by BRD4 depletion. In addition, the BET inhibitor NHWD-870 acted synergistically with trametinib to suppress melanoma growth in vitro and in vivo. Conclusions: We identified a new vulnerability for MEK inhibitor-resistant melanomas, which activated Hippo pathway due to elevated YAP1 activity. Inhibition of BRD4 using BET inhibitors suppressed YAP1 expression and led to blunted melanoma growth when combined with treatment with the MEK inhibitor trametinib.

[Preparation of Shuxiong pulsatile controlled-release dropping pill].

OBJECTIVE: To prepare Shuxiong pulsatile controlled-release dropping pill and study the influencing factors in vitro. METHODS: Dropping pills with suitable size (10 - 15 mg) were coated with swelling layer containing croscarmellose sodium and controlled-release layer containing ethylcellulos aqueous dispersion respectively to prepare Shuxiong pulsatile controlled-release dropping pill. The effects of the materials of swelling layer, the weight of swelling layer and controlled-release layer on the release of drugs were investigated to optimize the process technology and validate formula. RESULTS: The release behavior was influenced strikingly by the types and weight of coating layer. The optimal formula was as follows: Shuxiong pulsatile controlled-release dropping pills were prepared using croscarmellose sodium as inner layer with 15% (weight) coating level and ethylcellulose aqueous dispersion (Surelease) as outer controlled-release layer with 7% (weight) coating level. The lag time of prepared pulsatile controlled-release dropping pills was about 4 h and accumulative release rate reached 80% within 4 h. CONCLUSION: The drug release of Shuxiong pulsatile controlled-release dropping pill is shown in pulsatile way in vitro.

Integrated single-cell and bulk RNA sequencing analysis identified pyroptosis-related signature for diagnosis and prognosis in osteoarthritis.

Osteoarthritis (OA), a degenerative disease of the joints, has one of the highest disability rates worldwide. This study investigates the role of pyroptosis-related genes in osteoarthritis and their expression in different chondrocyte subtypes at the individual cell level. Using OA-related datasets for single-cell RNA sequencing and RNA-seq, the study identified PRDEGs and DEGs and conducted Cox regression analysis to identify independent prognostic factors for OA. CASP6, NOD1, and PYCARD were found to be prognostic factors. Combined Weighted Gene Correlation Network Analysis with PPI network, a total of 15 hub genes related to pyroptosis were involved in the notch and oxidative phosphorylation pathways, which could serve as biomarkers for the diagnosis and prognosis of OA patients. The study also explored the heterogeneity of chondrocytes between OA and normal samples, identifying 19 single-cell subpopulation marker genes that were significantly different among 7 chondrocyte cell clusters. AGT, CTSD, CYBC, and THYS1 were expressed differentially among different cell subpopulations, which were associated with cartilage development and metabolism. These findings provide valuable insights into the molecular mechanisms underlying OA and could facilitate the development of new therapeutic strategies for this debilitating disease.

[Optimize the preparation process of Erigeron breviscapus sustained-release pellets based on artificial neural network and particle swarm optimization algorithm].

OBJECTIVE: To optimize the preparation process of Erigeron breviscapus sustained-release pellets. METHODS: A mathematical model of relationship between the independent variables and dependent variable of the preparation process of Erigeron breviscapus sustained-release pellets was established by using back-propagation (BP) artificial neural networks (ANN), and the preparation process parameters were optimized with particle swarm optimization (PSO) algorithm. RESULTS: The pellets prepared according to the optimized preparation process parameters had significant effect of sustained-releasing. Drug release from the pellets was controlled by both diffusion and matrix corrosion. CONCLUSION: Combining BP ANN modeling with PSO algorithm provides an effective way to solve the multi-dimensional optimization problem of complicated nonlinear systems in pharmaceutical technology.

Effect of a 2-HP-ß-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles.

BACKGROUND: The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles. METHODS: PTX-loaded 2-HP-ß-CD-modified PLGA nanoparticles (2-HP-ß-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized. RESULTS: Compared with the plain PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-ß-CD/PLGA NPs was 2.4-fold higher than commercial Taxol® and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-ß-CD/PLGA NPs exhibited excellent stability in the circulation. CONCLUSION: The results of this study suggest that the formulation that contains 2-HP-ß-CD can prolong PTX release, enhance drug transport efficiency and serve as a potential tumor targeting system for PTX.

Preparation of clarithromycin floating core-shell systems (CSS) using multi-nozzle semi-solid extrusion-based 3D printing.

Matrix erosion is unavoidable during the release of poorly soluble drugs from gastric floating delivery system (GFDDS), which shortens the floating time and diminishes drug release. We fabricated a core-shell system (CSS) consisting of a low-density drug-loaded shell and a floating core using multi-nozzle semi-solid extrusion (SSE) 3D printing technology. The clarithromycin (CAM) loading capacity of the shell was 81.7%. The floating core paste provided structural support during printing and formed a hollow structure in CAM CSS, which increased the buoyancy in the early stage of drug release. In addition, the floating core had numerous micro-airbags that swelled when the solution penetrated the core, and generated CO2. The micro-airbag structure and CO2 generation further increased the buoyancy of CSS. The CAM CSS achieved 74.5% (w/w) drug loading, 8 h sustained release, and immediate and prolonged floating (>10 h). This structure of CSS and floating core provide a novel perspective for constructing a stable gastric floating drug delivery system.

Micro-interaction of mucin tear film interface with particles: The inconsistency of pharmacodynamics and precorneal retention of ion-exchange, functionalized, Mt-embedded nano- and microparticles.

Physiological reflexes and anatomical barriers render traditional eye drop delivery inefficient. We previously reported that drug-loaded nanoparticles and microspheres prepared from montmorillonite and Eudragit polymers exhibited good sustained-release and lowered intraocular pressure. Here, we compared the performance of optimized formulations to select the most suitable formulation for glaucoma therapy. We found that the microspheres had much higher encapsulation efficiency and drug loading than nanoparticles. Moreover, cytocompatibility experiments demonstrated that nanoparticles showed more severe cytotoxicity than microspheres, probably due to their smaller particles, enhanced cell uptake, and intracellular solubility. Interestingly, the pre-corneal retention time of nanoparticles reflected a clear advantage over microspheres, while the duration of the pharmacological effect of nanoparticles was not as good as that of microspheres: compared with the nanoparticle depressurization duration of only 8 h, the microspheres continuously depressurized for 12 h. The slower release of the microspheres and its micro-interaction mechanism with the discontinuous mucin layer of the tear film led to the inconsistency between duration of pharmacodynamics and fluorescence ocular retention time. In summary, the lower cytotoxicity and longer pharmacological effect of microspheres indicate their potential advantages for glaucoma applications.

Cross-linked thermosensitive nanohydrogels for ocular drug delivery with a prolonged residence time and enhanced bioavailability.

AIM: A temperature-triggered, cross-linked nano hydrogel formulation (NPs-gel) was prepared to prolong the residence time of dexamethasone (DXM) in the eye and increase its bioavailability. RESEARCH DESIGN AND METHODS: The NPs-gel was prepared by combining a high pressure homogenization method with a cold solution method. Soy lecithin E200, lecithin oil, glycerol, kolliphor P188, kolliphor P407, and polycarbophil were the excipients used for the formation of NPs-gel containing DXM. The nanoparticle size, temperature-sensitive phase transition characteristics, in vitro and in vivo release behavior, corneal permeability, and eye irritation level of the NPs-gel were evaluated. RESULTS: The NPs-gel had slightly larger particle size than the DXM-loaded nanoparticles, yet it retained the properties of nanoparticles such as surface effect and size effect. The phase transition temperature was 33.2 °C, which is within the trigger conditions of intraocular temperature. Under physiological conditions, the adhesion and adhesion work of the NPs-gel were 1.1 and 2.1 times that of an in situ-formed gel, and the gel strength of NPs-gel was 1.8 times that of an in situ-formed gel. These results indicate that NPs-gel has greater adhesion and mechanical strength. The area under the curve of NPs-gel was 3.08 and 1.51 times that of DXM-loaded nanoparticles and in situ-formed gel, showing higher bioavailability. CONCLUSION: The NPs-gel is a suitable formulation to further enhance ocular drug delivery.

Compact high-efficiency 100-W-level diode-side-pumped Nd:YAG laser with linearly polarized TEM00 mode output.

We present a compact high-efficiency and high-average-power diode-side-pumped Nd:YAG rod laser oscillator operated with a linearly polarized fundamental mode. The oscillator resonator is based on an L-shaped convex-convex cavity with an improved module and a dual-rod configuration for birefringence compensation. Under a pump power of 344 W, a linearly polarized average output power of 101.4 W at 1064 nm is obtained, which corresponds to an optical-to-optical conversion efficiency of 29.4%. The laser is operated at a repetition rate of 400 Hz with a beam quality factor of M(2)=1.14. To the best of our knowledge, this is the highest optical-to-optical efficiency for a side-pumped TEM(00) Nd:YAG rod laser oscillator with a 100-W-level output ever reported.

[Study on formulation of naoxuekang dispersible tablets].

OBJECTIVE: To study the formulation of Naoxuekang dispersible tablets. METHODS: The formulation was determined by pre-processing leech extractum prior to a series of experiments used to screen excipients like bulking agents and disintegrants and so on, and by adding disintegrants within and without. RESULTS: Microcrystalline cellulose was determined as the bulking agent, and carboxymethyl cellulose and low-substituted hydroxypropyl cellulose were determined as the disintegrants of Naoxuekang dispersible tablet formula. The average disintegration time and nitrogen content of one tablet were 52 seconds and 5.47 milligrams, respectively. Also disperse homogeneity, weight variation and microbial limit all met the requirements in Ch. P. CONCLUSION: The prepared Naoxuekang dispersible tablet is reasonable in formula, feasible in technology, which meets the quality standards.

Enhancing Betulinic Acid Dissolution Rate and Improving Antitumor Activity via Nanosuspension Constructed by Anti-Solvent Technique.

PURPOSE: The aim of this study was to prepare and evaluate betulinic acid nanosuspension (BA-NS) for new drug delivery to enhance its solubility and in vitro anti-tumor activity. METHODS: BA-NS was formulated by an anti-solvent precipitation method using the Box-Behnken design (BBD). Particle size (PS) and Zeta potential were measured by laser particle size analysis. The drug solid state after freeze drying was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) after freeze drying. The saturation solubility and dissolution rate were determined by solubility assay and in vitro dissolution studies, respectively. The in vitro cytotoxicity assay was performed using 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) method. RESULTS: The PS was 129.7±12.2 nm having a Zeta potential of -28.1±4.5 mV and the polydispersity index (PDI) was 0.231±0.013, which confirmed that the nanosuspension was in the stable amorphous state. A series of characterization experiments demonstrated that nanoparticles retained original effective structure and existed as spherical or near-spherical nanoparticles in the nanosuspension, but the drug transferred from the crystal state to the amorphous state. The form of lyophilized BA-NS was very successful in enhancing the dissolution rate in PH-dependent way. The cytotoxicity assay revealed that BA-NS could significantly enhance the in vitro anti-proliferation against tumor cells compared to the BA suspension (BA-S). CONCLUSION: The BA-NS can remarkably improve solubility and in vitro antitumor activity, which seems very promising for the treatment of cancers in practical application.

Incorporation of ion exchange functionalized-montmorillonite into solid lipid nanoparticles with low irritation enhances drug bioavailability for glaucoma treatment.

Montmorillonite-loaded solid lipid nanoparticles with good biocompatibility, using Betaxolol hydrochloride as model drug, were prepared by the melt-emulsion sonication and low temperature-solidification methods and drug bioavailability was significantly improved in this paper for the first time to application to the eye. The appropriate physical characteristics were showed, such as the mean particle size, Zeta potential, osmotic pressure, pH values, entrapping efficiency (EE%) and drug content (DC%), all showed well suited for possible ocular application. In vitro release experiment indicated that this novel system could continuously release 57.83% drugs within 12 h owing to the dual drug controlled-release effect that was achieved by ion-exchange feature of montmorillonite and structure of solid lipid nanoparticles. Low irritability and good compatibility of nanoparticles were proved by both CAM-TBS test and cytotoxicity experiment. We first discovered from the results of Rose Bengal experiment that the hydrophilicity of the drug-loaded nanoparticles surface was increased during the loading and releasing of the hydrophilic drug, which could contribute to prolong the ocular surface retention time of drug in the biological interface membrane of tear-film/cornea. The results of in vivo pharmacokinetic and pharmacodynamics studies further confirmed that increased hydrophilicity of nanoparticles surface help to improve the bioavailability of the drug and reduce intraocular pressure during administration. The results suggested this novel drug delivery system could be potentially used as an in situ drug controlled-release system for ophthalmic delivery to enhance the bioavailability and efficacy.