Design and synthesis of drug hydrogels containing carboxymethylcellulose with honeycomb structure and pH-sensitivity as drug delivery systems for adriamycin, metformin, and naproxen.

The aim of this research is to prepare and identify functionalized carboxymethylcellulose/mesoporous silica nanohydrogels (CMC/NH2-MCM-41) for obtaining a pH-sensitive system for the controlled release of drugs. The beads of CMC/NH2-MCM-41 nanocomposites were prepared by dispersing NH2-MCM-41 in a CMC polymer matrix and crosslinking with ferric ions (Fe3+). The SEM analysis of samples revealed enhancement in surface porosity of the functionalized nanohydrogel beads compared to the conventional beads. Swelling of the prepared functionalized nanohydrogels was evaluated at various pH values including pH = 7.35-7.45 (simulated body fluid or healthy cells), pH = 6 (simulated intestinal fluid), and pH = 1.5-3.5 (simulated gastric fluid). The swelling of CMC/MCM-41 and CMC/NH2-MCM-41 nanohydrogels at the pH values of simulated body fluid and simulated intestinal fluid is much higher than that of simulated gastric fluid, indicating successful synthesis of pH-sensitive nanohydrogels for drug delivery. The drug loading results showed that drug release in the CMC/NH2-MCM-41 system is much slower than that in the CMC/MCM-41 system. The results of the survival studies for the manufactured systems showed a very good biocompatibility of the designed drug delivery systems for biological applications. By coating the surface of functionalized mesopores with CMC hydrogel, we were able to develop a pH-sensitive intelligent drug delivery system.

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation.

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0-24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½ß, and the first-order rate constant for the elimination process ß in FN compared to non-FN patients. Furthermore, AUC0-24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0-24, which may require specific consideration during the treatment initiation.

Knowledge of and Testing Rate for Hepatitis C Infection among the General Public of Saudi Arabia: A Cross-Sectional Study.

INTRODUCTION: The Ministry of Health in Saudi Arabia has announced a plan to eradicate hepatitis C virus (HCV) infection. This study sought to evaluate the knowledge levels and testing rate among the general population of Saudi Arabia. METHODS: A cross-sectional study was conducted using data collected from an online, self-administered survey. Multivariable analysis was conducted using multiple binary logistic regression models to identify factors associated with low knowledge levels as well as predictors of HCV testing. RESULTS: A total of 689 participants completed the survey. While most participants (88%) have heard of HCV infection, less than half (47.3%) understood that HCV is curable with medications. More than half of the participants (53.7%) have low knowledge about HCV infection. Testing for HCV was reported by 123 respondents (17.8%), and the odds of testing for HCV were significantly lower among residents of the Makkah region (OR = 0.59 [95% CI: 0.36-0.97]) and those with low knowledge level (OR = 0.47 [95% CI: 0.29-0.74]). HCV diagnosis was reported by nine respondents (1.3%), of whom only four reported receiving treatment (44%). CONCLUSIONS: Our study indicates inadequate knowledge levels and relatively low testing rate. These findings underscore the need for national awareness campaigns and more effective strategies for HCV screening.

The Bayesian-Based Area under the Curve of Vancomycin by Using a Single Trough Level: An Evaluation of Accuracy and Discordance at Tertiary Care Hospital in KSA.

The AUC0-24 is the most accurate way to track the vancomycin level while the Cmin is not an accurate surrogate. Most hospitals in Saudi Arabia are under-practicing the AUC-guided vancomycin dosing and monitoring. No previous work has been conducted to evaluate such practice in the whole kingdom. The current study objective is to calculate the AUC0-24 using the Bayesian dosing software (PrecisePK), identify the probability of patients who receive the optimum dose of vancomycin, and evaluate the accuracy and precision of the Bayesian platform. This retrospective study was conducted at King Abdulaziz medical city, Jeddah. All adult patients treated with vancomycin were included. Pediatric patients, critically ill patients requiring ICU admission, patients with acute renal failure or undergoing dialysis, and febrile neutropenic patients were excluded. The AUC0-24 was predicted using the PrecisePK platform based on the Bayesian principle. The two-compartmental model by Rodvold et al. in this platform and patients' dose data were utilized to calculate the AUC0-24 and trough level. Among 342 patients included in the present study, the mean of the estimated vancomycin AUC0-24 by the posterior model of PrecisePK was 573 ± 199.6 mg, and the model had a bias of 16.8%, whereas the precision was 2.85 mg/L. The target AUC0-24 (400 to 600 mg·h/L) and measured trough (10 to 20 mg/L) were documented in 127 (37.1%) and 185 (54%), respectively. Furthermore, the result demonstrated an increase in odds of AUC0-24 > 600 mg·h/L among trough level 15-20 mg/L group (OR = 13.2, p < 0.05) as compared with trough level 10-14.9 mg/L group. In conclusion, the discordance in the AUC0-24 ratio and measured trough concentration may jeopardize patient safety, and implantation of the Bayesian approach as a workable alternative to the traditional trough method should be considered.

Formulation development of lipid polymer hybrid nanoparticles of doxorubicin and its in-vitro, in-vivo and computational evaluation.

The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (-9.33 to -18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.

PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases.

Research on the use of biodegradable polymers for drug delivery has been ongoing since they were first used as bioresorbable surgical devices in the 1980s. For tissue engineering and drug delivery, biodegradable polymer poly-lactic-co-glycolic acid (PLGA) has shown enormous promise among all biomaterials. PLGA are a family of FDA-approved biodegradable polymers that are physically strong and highly biocompatible and have been extensively studied as delivery vehicles of drugs, proteins, and macromolecules such as DNA and RNA. PLGA has a wide range of erosion times and mechanical properties that can be modified. Many innovative platforms have been widely studied and created for the development of methods for the controlled delivery of PLGA. In this paper, the various manufacturing processes and characteristics that impact their breakdown and drug release are explored in depth. Besides different PLGA-based nanoparticles, preclinical and clinical applications for different diseases and the PLGA platform types and their scale-up issues will be discussed.

Olive Leaf Extracts for a Green Synthesis of Silver-Functionalized Multi-Walled Carbon Nanotubes.

Green biosynthesis, one of the most dependable and cost-effective methods for producing carbon nanotubes, was used to synthesize nonhazardous silver-functionalized multi-walled carbon nanotubes (SFMWCNTs) successfully. It has been shown that the water-soluble organic materials present in the olive oil plant play a vital role in converting silver ions into silver nanoparticles (Ag-NPs). Olive-leaf extracts contain medicinal properties and combining these extracts with Ag-NPs is often a viable option for enhancing drug delivery; thus, this possibility was employed for in vitro treating cancer cells as a proof of concept. In this study, the green technique for preparing SFMWCNTs composites using plant extracts was followed. This process yielded various compounds, the most important of which were Hydroxytyrosol, Tyrosol, and Oleuropein. Subsequently, a thin film was fabricated from the extract, resulting in a natural polymer. The obtained nanomaterials have an absorption peak of 419 nm in their UV-Vis. spectra. SEM and EDS were also used to investigate the SFMWCNT nanocomposites' morphology simultaneously. Moreover, the MTT assay was used to evaluate the ability of SFMWCNTs to suppress cancer cell viability on different cancer cell lines, MCF7 (human breast adenocarcinoma), HepG2 (human hepatocellular carcinoma), and SW620 (human colorectal cancer). Using varying doses of SFMWCNT resulted in the most significant cell viability inhibition, indicating the good sensitivity of SFMWCNTs for treating cancer cells. It was found that performing olive-leaf extraction at a low temperature in an ice bath leads to superior results, and the developed SFMWCNT nanocomposites could be potential treatment options for in vitro cancer cells.

Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies.

INTRODUCTION: Vancomycin administration in individuals with hematological malignancy or neutropenia is associated with a suboptimal trough concentration. Nonetheless, most studies did not distinguish whether low vancomycin trough concentrations were due to hematological malignancies or neutropenia. This study aimed to determine the association between types of hematological malignancy and febrile neutropenia with low vancomycin concentrations. METHODS: The present retrospective chart review study was conducted by using clinical data adopted from computerized physician order entries (BestCare®) for all of the patients who received intravenous vancomycin treatment between January 2017 and December 2020 at King Abdulaziz Medical City in Jeddah. RESULTS: Out of the 296 patients, 217 were included. There was no significant association between the type of hematological malignancy and the incidence of a low trough concentration (p > 0.05), while a significant association between febrile neutropenia and the incidence of a low trough concentration was observed (p < 0.05). Furthermore, the predictors for a low trough among febrile neutropenic patients were creatinine clearance (CrCI) and a low albumin concentration. In addition, there was a significant association between febrile neutropenia and augmented renal clearance (p < 0.05). CONCLUSIONS: The findings of this study conclude that febrile neutropenia is associated with low vancomycin concentrations. Interestingly, augmented renal clearance was observed in most of the febrile neutropenia patients with a significant association, which is considered the main driver for a low trough in neutropenic patients.

Construction of a binary S-scheme S-g-C3N4/Co-ZF heterojunction with enhanced spatial charge separation for sunlight-driven photocatalytic performance.

A step-scheme (S-scheme) photocatalyst made of sulfurized graphitic carbon nitride/cobalt doped zinc ferrite (S-g-C3N4/Co-ZF) was constructed using a hydrothermal process because the building of S-scheme systems might increase the lifespan of highly reactive charge carriers. Utilizing cutting-edge methods, the hybrid photocatalyst was evaluated by employing TEM, XPS, XRD, BET, FTIR, transient photo-response, UV-vis, EIS and ESR signals. In order to create a variety of binary nanocomposites (NCs), nanoparticles (NPs) of 6% cobalt doped zinc ferrite (Co-ZF) were mixed with S-g-C3N4 at various concentrations, ranging from 10 to 80 wt%. For photocatalytic dye removal, a particular binary NC constructed between S-g-C3N4 and Co-ZF produces a huge amount of catalytic active sites. The findings showed that loading of S-g-C3N4 on 6% Co-ZF NPs serves as a good heterointerface for e-/h+ separation and transportation through the S-scheme S-g-C3N4/Co-ZF heterojunction. By boosting the hybrid system's BET surface area for the photocatalytic process, the addition of 6% Co-ZF improves the system's ability to absorb more sunlight and boosts its photocatalytic activity. The highest photo-removal effectiveness (98%), which is around 2.45 times higher than that of its competitors, was achieved by the hybrid photocatalyst system with an ideal loading of 48% Co-ZF. Furthermore, the trapping studies showed that the primary species involved in the MB aqueous photo-degradation were ˙OH- and h+.

Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing.

Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.

Efficacy of Various Types of Berries Extract for the Synthesis of ZnO Nanocomposites and Exploring Their Antimicrobial Potential for Use in Herbal Medicines.

Nanoscience has developed various greener approaches as an alternate method for the synthesis of nanoparticles and nanocomposites. The present study discusses the efficacy of berries extract for the synthesis of ZnO nanocomposites. Characterization of synthesized nanocomposite were done by SEM, UV/VIS spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, and XRD techniques. The crystalline nature of the synthesized nanoparticles was verified by XRD pattern in the range of 10-80 nm. The UV absorption peak of Elaeagnus umbellata (ZnO-EU) nanocomposite at 340 nm, Rubus idaeus (ZnO-Ri) nanocomposite at 360 nm, and Rubus fruticosus (ZnO-Rf) nanocomposite at 360 nm was observed. The nanocomposites were analyzed for their antimicrobial activity and found to be effective against three phytopathogens. The antimicrobial activity of ZnO nanocomposites showed good results against Escherichia coli (341), Staphylococcus aureus (345B), and Pseudomonas aeruginosa (5994 NLF). This study presents a simple and inexpensive approach for synthesizing zinc oxide nanocomposites with effective antibacterial activity.

Biocompatibility and Hemolytic Activity Studies of Synthesized Alginate-Based Polyurethanes.

Many investigators have focused on the development of biocompatible polyurethanes by chemical reaction of functional groups contained in a spacer and introduced in the PU backbone or by a grafting method on graft polymerization of functional groups. In this study, alginate-based polyurethane (PU) composites were synthesized via step-growth polymerization by the reaction of hydroxyl-terminated polybutadiene (HTPB) and hexamethylene diisocyanate (HMDI). The polymer chains were further extended with blends of 1,4-butanediol (1,4-BDO) and alginate (ALG) with different mole ratios. The structures of the prepared PU samples were elucidated with FTIR and 1H NMR spectroscopy. The crystallinity of the prepared samples was evaluated with the help of X-ray diffraction (XRD). The XRD results reveal that the crystallinity of the PU samples increases when the concentration of alginate increases. Thermogravimetric (TGA) results show that samples containing a higher amount of alginate possess higher thermal stability. ALG-based PU composite samples show more biocompatibility and less hemolytic activity. Mechanical properties, contact angle, and water absorption (%) were also greatly affected.

Causes of vancomycin dosing error; problem detection and practical solutions; a retrospective, single-center, cross-sectional study.

Vancomycindosing error and inappropriate monitoring is a common problem in hospital daily practice. In King Abdulaziz Medical City (KAMC) in Jeddah, a high percentage of abnormal vancomycin trough levels is still detected despite using the recommended dose. Therefore, the current research objective is to study the major causes of vancomycin dosing errors. This retrospective, single-center, cross-sectional study was carried out at KAMC hospital in Jeddah from January 1st until December 31st 2019. All adult patients (≥15 years) who received vancomycin and had an initial abnormal trough level at the measured steady-state were included in this study. 472 patients have met the study inclusion criteria. The current study evaluated the factors that play a role in causing vancomycin trough level abnormalities such as sampling time, vancomycin dosing, and patient's pharmacokinetic and pharmacodynamic variations. In this study, we found that pharmacokinetic and pharmacodynamic variability was attributed to 65% of vancomycin's abnormal trough level. Also, the result showed a significantly increased odds of the low trough in the non-elderly group (OR 6, 95% CI 2.48 - 14.9, P < 0.001) and febrile neutropenic patients (OR 2.21, 95% CI 1.119 - 4.365, P < 0.05). However, the odds of high trough levels were significantly elevated among patients who have CrCl < 50 ml/min (OR 5, 95% CI 1.262-20.539, P < 0.05). In addition, the present investigation revealed that the occurrence of abnormal vancomycin levels was not affected by daily duty time or working days (p > 0.05). The current study indicated that vancomycin dosing errors were common in KAMC patients; thus, there is an unmet need to evaluate the causes of vancomycin abnormal trough level and optimize a strategy that would enhance the therapeutic effectiveness and minimize the potential toxicity.

Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages.

Drug resistance is one of the significant clinical burden in renal cell carcinoma (RCC). The development of drug resistance is attributed to many factors, including impairment of apoptosis, elevation of carbonic anhydrase IX (CA IX, a marker of tumor hypoxia), and infiltration of tumorigenic immune cells. To alleviate the drug resistance, we have used Sorafenib (Sor) in combination with tumor hypoxia directed nanoparticle (NP) loaded with a new class of apoptosis inducer, CFM 4.16 (C4.16), namely CA IX-C4.16. The NP is designed to selectively deliver the payload to the hypoxic tumor (core), provoke superior cell death in parental (WT) and Everolimus-resistant (Evr-res) RCC and selectively downmodulate tumorigenic M2-macrophage. Copper-free 'click' chemistry was utilized for conjugating SMA-TPGS with Acetazolamide (ATZ, a CA IX-specific targeting ligand). The NP was further tagged with a clinically approved NIR dye (S0456) for evaluating hypoxic tumor core penetration and organ distribution. Imaging of tumor spheroid treated with NIR dye-labeled CA IX-SMA-TPGS revealed remarkable tumor core penetration that was modulated by CA IX-mediated targeting in hypoxic-A498 RCC cells. The significant cell killing effect with synergistic combination index (CI) of CA IX-C4.16 and Sor treatment suggests efficient reversal of Evr-resistance in A498 cells. The CA IX directed nanoplatform in combination with Sor has shown multiple benefits in overcoming drug resistance through (i) inhibition of p-AKT, (ii) upregulation of tumoricidal M1 macrophages resulting in induction of caspase 3/7 mediated apoptosis of Evr-res A498 cells in macrophage-RCC co-culturing condition, (iii) significant in vitro and in vivo Evr-res A498 tumor growth inhibition as compared to individual therapy, and (iv) untraceable liver and kidney toxicity in mice. Near-infrared (NIR) imaging of CA IX-SMA-TPGS-S0456 in Evr-res A498 RCC model exhibited significant accumulation of CA IX-oligomer in tumor core with >3-fold higher tumor uptake as compared to control. In conclusion, this proof-of-concept study demonstrates versatile tumor hypoxia directed nanoplatform that can work in synergy with existing drugs for reversing drug-resistance in RCC accompanied with re-education of tumor-associated macrophages, that could be applied universally for several hypoxic tumors.

Development and Evaluation of a Novel Microemulsion of Dexamethasone and Tobramycin for Topical Ocular Administration.

PURPOSE: The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections. METHODS: The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex®). Histological evaluation was performed in bovine corneas to assess the safety of microemulsion in comparison to Tobradex suspension. In addition, the stability of the microemulsion was studied at 4°C, 25°C, and 40°C. RESULTS: The pH of the microemulsion was close to the pH of tear fluid. The microemulsion displayed an average globule size under 20 nm, with light transmittance around 95%-100%. The aseptically prepared microemulsion remained sterile for up to 14 days. The cytotoxicity of the microemulsion in bovine corneal endothelial cells was comparable to that of the Tobradex suspension. The anti-inflammatory activity of dexamethasone and the antibacterial activity of tobramycin from the microemulsion were significantly higher than those of the Tobradex suspension (P < 0.05). Histological evaluation showed an intact corneal epithelium without any signs of toxicity, and the developed microemulsion was found to be stable at 4°C and 25°C for 3 months. CONCLUSION: In conclusion, the developed microemulsion could be explored as a suitable alternative to the marketed suspension for treating anterior segment eye infections.

Tanshinone IIA Inhibits VEGF Secretion and HIF-1α Expression in Cultured Human Retinal Pigment Epithelial Cells under Hypoxia.

PURPOSE: The current work intends to study the activity of tanshinone IIA on secretion of vascular endothelial growth factor (VEGF) and expression of hypoxia inducible factor 1α (HIF-1α) in human retinal pigment epithelial cells (ARPE-19 cells) under hypoxic condition. METHODS: The cytotoxicity of tanshinone IIA was tested in ARPE-19 cells by MTT assay. ARPE-19 cells were incubated with different concentrations of cobalt chloride (100, 150, and 200 µM) for 12 h, and levels of expressed HIF-1α and secreted VEGF were quantified through Western blot and ELISA, respectively. Further, ARPE-19 cells were pretreated for 1 h with different concentrations of tanshinone IIA (5, 10, 15, and 18 µM). After 1 h, the cells were subjected to hypoxic condition using 150 µM cobalt chloride for 12 h in the presence and absence of tanshinone IIA. The cells were then harvested, and the secreted VEGF and expressed HIF-1α was studied. RESULTS: Tanshinone IIA at concentrations of 5, 10, 15, and 18 µM did not show cytotoxicity in ARPE-19 cells. Chemical hypoxia induced by cobalt chloride caused a significant increase in VEGF level in a dose-dependent manner, and HIF-1α expression peaked at 150 µM. Based on the data, cobalt chloride concentration was maintained at 150 µM for further studies. Tanshinone IIA decreased the level of HIF-1α and VEGF secretion in a dose-dependent manner under hypoxic condition. CONCLUSION: Tanshinone IIA could be explored as a new potential candidate for treating wet AMD.

Comparison of electrospun and solvent cast polylactic acid (PLA)/poly(vinyl alcohol) (PVA) inserts as potential ocular drug delivery vehicles.

PURPOSE: The purpose of this work was to develop, characterize and compare electrospun nanofiber inserts (ENIs) and solvent cast polymeric inserts (SCIs) for ocular drug delivery. METHODS: ENI and SCI of 1%, 5% and 10% w/w dexamethasone were fabricated using a blend of poly-lactic acid (PLA) and poly-vinyl alcohol (PVA). Inserts were characterized for morphology, thickness, pH, drug content, drug crystallinity, in vitro drug release, sterility, dimethylformamide (DMF) and chloroform content, and cytotoxicity. RESULTS: The thickness of 1%, 5%, and 10% dexamethasone-loaded ENIs were found to be 50µm, 62.5µm, and 93.3µm, respectively, with good folding endurance. SCIs were brittle, with thickness values >200µm. Drug release rates from 1%, 5% and 10% ENIs were found to be 0.62µg/h, 1.46µg/h, and 2.30µg/h, respectively, while those from SCIs were erratic. DMF content in ENIs and SCIs were 0.007% w/w and 0.123% w/w, respectively, while chloroform was not detected. No cytotoxicity was observed from ENIs in cultured bovine corneal endothelial cells for up to 24h. CONCLUSION: We conclude that ENIs are better than SCIs and could be utilized as a potential delivery system for treating anterior segment ocular diseases.

Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma.

The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by ¹H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC) for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI-RB) retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19), indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies.

Formulation and In Vitro Evaluation of Cyclosporine-A Inserts Prepared Using Hydroxypropyl Methylcellulose for Treating Dry Eye Disease.

PURPOSE: The aim of this study was to develop and characterize a novel sustained-release drug delivery system of cyclosporine-A (CsA) using hydroxypropyl methylcellulose (HPMC) and xanthan gum (XG) for treating dry eye disease (DED). METHODS: Polymeric inserts of CsA were prepared using the solvent casting technique with a 2(3) full factorial design to evaluate the effect of HPMC and XG ratios and drug content on thickness, folding endurance, wettability, and in vitro drug release. Inserts were also evaluated for drug content, moisture absorption and loss, and surface pH. Inserts with an optimized ratio of HPMC and XG were sterilized with UV light and evaluated for morphology, thermal analysis, Fourier transform infrared spectroscopy, stability at 4°C, 25°C, and 40°C, cytotoxicity in cultured bovine corneal endothelial cells, and anti-inflammatory effect in Jurkat T cells. RESULTS: The addition of XG increased the CsA release duration and enhanced the folding endurance of films. All films showed uniformity in drug content and thickness. Formulation F4 composed of 1% HPMC and 0.25% XG exhibited good folding endurance and sustained CsA release for up to 20 h. Sterility testing of F4 using plate and direct inoculation confirmed the formulation sterility and validated the sterilization method. The formulation was stable for at least 3 months at 4°C, 25°C, and 40°C. No cytotoxicity was observed in cultured bovine corneal endothelial cells for up to 24 h. The anti-inflammatory effect of CsA was intact in ophthalmic inserts. CONCLUSION: In conclusion, combination therapy with HPMC and CsA can be a potential once-a-day formulation for treating DED.

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin.

OBJECTIVE: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life. METHODS: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (Css) of chlorpromazine was calculated from the flux values. RESULTS: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical Css of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50 ng/ml, respectively. PLO gels only marginally increased the flux and theoretical Css of chlorpromazine. CONCLUSION: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.