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Hydrocephalus is a neurological disease caused by an unusually high level of cerebrospinal fluid (CSF), which can be relieved by external ventricular drainage (EVD) insertion. However, the infection can lead to complications during the use of EVD. In this study, EVD was impregnated with three synergistic antibiotics, including rifampicin, clindamycin, and trimethoprim, to improve the antibacterial property. The impregnated drainage was studied for its characteristics in vitro and in vivo. Drug loading determination revealed that rifampicin had the highest concentration in the tube, followed by clindamycin and trimethoprim, respectively. In vitro cytotoxicity and hemolytic studies showed no toxic effects from antibiotics-impregnated EVD on fibroblast and red blood cells. For antibacterial testing, the impregnated EVD exhibited antibacterial activity against Staphylococcus aureus MRSA and Staphylococcus epidermidis up to 14 and 90 days, respectively. Moreover, biocompatibility and drug release into the bloodstream and surrounding tissues were investigated by implantation in rabbits for 30 days. Histology and morphology results showed that fibroblast cells began to adhere to the drainage surface and inflammatory cell numbers were noticeably small after the long-term implantation. In addition, there was no drug leakage to the bloodstream and surrounding tissues. Hence, this impregnated EVD can potentially be used for antibacterial application. [ABSTRACT FROM AUTHOR]

Chronic wounds, such as burns and diabetic ulcers, are complex wounds sustained by the skin that require life-long rehabilitation and have the potential to deteriorate and get infected. The number of patients with this ailment has been steadily increasing. This illness demands the use of new dressings with the best capabilities for managing wound healing. This study created an gel with carboxymethylcellulose (CMC), hyaluronic acid (HA), and zinc oxide nanoparticles (ZnO NPs). According to the findings, the manufacturing technique with a 1:4 ratio of HA and CMC gel had the best viscosity. Additionally, varying concentrations of zinc oxide nanoparticles (ZnO NPs) were added to the formula. Variations included 0.05, 0.125, 0.5, 1.0, 3.0, 5.0, and 10% by weight. In order to find the ideal dose and formulation, physical properties, an anti-bacterial test, and a cell migration assay were carried out. The samples with concentration of 0.5, 1.0, 3.0, 5.0 and 10% w/v showed ability to kill gram-positive and gram-negative bacteria. Wound healing experiments showed that cells proliferated for HA/CMC/ZnO gel with a weight-to-volume ratio of 0.05% and 1.0% w/v. In conclusion, according to all (physical and biological) characterization, the HA/CMC/ZnO gel with a weight-to-volume ratio of 1.0% w/v was found to have a considerable standard for wound-healing materials, demonstrating a promising effect against bacteria. [ABSTRACT FROM AUTHOR]

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer. [ABSTRACT FROM AUTHOR]

We report a simple and rapid method for the synthesis of fluorescent gallium oxyhydroxide (GaOOH) nanoparticles from liquid Ga by a probe sonication method in the presence of H2O2 as an oxidant. The aspect ratio of the GaOOH nanoparticles is determined by the concentration of H2O2 and solution pH, as well as the probe energy and sonication time. Further surface modification with cyclodextrin to achieve biocompatibility for potential biomedical applications is reported where an example of cell uptake and fluorescence imaging is shown. [ABSTRACT FROM AUTHOR]

PCSK9 is a promising target for developing novel cholesterol-lowering drugs. We developed a recipe that combined molecular docking, GC-MS/MS, and real-time PCR to identify potential PCSK9 inhibitors for herb ratio determination. Three herbs, Carthamus tinctorius, Coscinium fenestratum, and Zingiber officinale, were used in this study. This work aimed to evaluate cholesterol-lowering through a PCSK9 inhibitory mechanism of these three herbs for defining a suitable ratio. Chemical constituents were identified using GC-MS/MS. The PCSK9 inhibitory potential of the compounds was determined using molecular docking, real-time PCR, and Oil red O staining. It has been shown that most of the active compounds of C. fenestratum and Z. officinale inhibit PCSK9 when extracted with water, and C. fenestratum has been shown to yield tetraacetyl-d-xylonic nitrile (27.92%) and inositol, 1-deoxy-(24.89%). These compounds could inhibit PCSK9 through the binding of 6 and 5 hydrogen bonds, respectively, while the active compound in Z. officinale is 2-Formyl-9-[.beta.-d-ribofuranosyl] hypoxanthine (4.37%) inhibits PCSK9 by forming 8 hydrogen bonds. These results suggest that a recipe comprising three parts C. fenestratum, two parts Z. officinale, and one part C. tinctorius is a suitable herbal ratio for reducing lipid levels in the bloodstream through a PCSK9 inhibitory mechanism. [ABSTRACT FROM AUTHOR]

Andrographolide is a group of diterpenoid lactone isolated from Andrographis paniculata (Burm. F.) NEES. One of the analogues is 19-O-triphenylmethylandrographolide (RSPP050) which possesses anticancer activity. In seeking to capitalise on the last property, we have investigated the in vitro tumour targeting capabilities and MRI imaging for hepatocellular carcinoma. In this study, we have designed galactose-targeted and non-targeted micelles comprised of poly(ethylene glycol)-b-poly(lactide) that enveloped RSPP050 as an anticancer agent and superparamagnetic iron oxide (SPIO) as a contrast agent. The targeting abilities were endeavored by examining the cellular uptake with MTT assay, fluorescence microscopy, Prussian blue staining, and in vitro MRI. Targeted SPIO micelles as a T2* contrast agent decreased the relative T2* MRI intensity at 3 h. Results revealed that galactose micelles displayed 10.91 ± 0.19% drug loading content, −37.17 ± 0.63 mV zeta potential, and these micelles at the concentration of 0.5 µg/ml exhibited higher cytotoxicity than non-targeted micelles and free RSPP050 after incubation for 24 h. Fluorescence microscopy and Prussian blue staining at 3 h demonstrated significant cellular uptake by HepG2 cells. Thus, anticancer activity of RSPP050 could be improved using galactose as a targeting ligand and theranostic function was achieved using SPIO. [ABSTRACT FROM AUTHOR]

Two types of nanospheres, namely clindamycin-loaded nanospheres (CN) and rifampicin-loaded nanospheres (RN) were successfully prepared using emulsion solvent evaporation technique. Poly(ε-caprolactone-random-d,l-lactide)-block-poly(ethylene glycol)-block-poly(ε-caprolactone-random-d,l-lactide) (PLEC) was used for preparing nanospheres. CN and RN were coated on an antibiotic-impregnated silicone tube surface by spray coating technique. The formulations of antibiotic-loaded nanospheres (CN and RN) and the amount of spray coating cycles were optimized. Drug-loading content (DLC), encapsulation efficiency, zeta potential, and size of nanospheres were characterized. The optimal ratios of PLEC to clindamycin; and PLEC to rifampicin were both at 2:1. Drug-loading contents of CN and RN were 2.62 ± 0.04% and 7.02 ± 0.02%, respectively. The optimum coating of 90 cycles was provided DLCs of 0.0637 ± 0.033 wt.% and 0.0613 ± 0.018 wt.% for rifampicin and clindamycin, respectively. The coating of silicone tube was able to prolong the release of both antibiotics for at least 30 days. Antibacterial activity test was performed using MRSA (ATCC 43300) and S. Epidermidis (ATCC 12228). Moreover, the cytotoxicity of antibiotic-loaded nanospheres coated on silicone tubes was evaluated. The coated silicone tube showed antibacterial activity for at least 28 days and was biocompatible with L929 cells. [ABSTRACT FROM AUTHOR]

Foley urinary catheters were coated with chlorhexidine‐loaded nanoparticles (CHX‐NPs), encapsulated in the form of micelles and nanospheres. Both of nanoparticles were deposited by multilayer nanocoating through dip and spray coating on the catheter surface both inner and outer surface. In our previous studies, the nanocoating of Foley urinary catheters was studied for chlorhexidine release, degradation, antibacterial evaluation, cytotoxicity assessment, hemocompatibility, skin irritation, skin sensitization, and stability during storage. The results demonstrated the antimicrobial functions and biocompatibility of the coated catheters. In this study, coated urinary catheters were inserted in the bladders of rabbits for 7 day to investigate their efficacy. Histopathology results showed no inflammation, redness, or swelling on bladder and urethra tissues. Surface morphology comparison of uncoated catheters in the control group and coated catheters in the treatment group revealed more encrustation and crystallization on uncoated catheter than on coated catheter, indicating that catheters coated with CHX‐NPs showed efficacy in delaying encrustation and bacterial colonization. These findings suggest that nanocoating of urinary catheters can potentially enhance the biocompatibility of medical devices. [ABSTRACT FROM AUTHOR]

MUC-30 is a hydrophobic compound which is active against the MCF-7 cancer cell line. In this study, MUC-30 was loaded in polymeric micelles to improve the water solubility and release rate. For prolonged MUC-30 release, MUC-30 was encapsulated in polymeric micelles using PEG-b-PLA and PEG-b-PCL as materials. Micelles prepared with 1 : 9 w per w ratios by film hydration achieved the highest entrapment efficiency (EE%). The EE% of MUC-30-loaded PEG-b-PCL micelles was approximately 30% greater than that of PEG-b-PLA micelles, due to the different H-bond formations between MUC-30 and the polymer membrane (PCL, 4; PLA, 3). The cytotoxic activity of MUC-30 against EGFR theoretically presented 399.31 nM (IC50 = 282.26 ng/mL) by molecular docking. In vitro cytotoxic activity of MUC-30 was confirmed by MTT assay. MUC-30 (IC50 = 11 ± 0.39 ng/mL) showed three-fold higher activity over MUC-30-loaded PEG-b-PLA micelles (IC50 = 37 ± 1.18 ng/mL) and two-fold higher over PEG-b-PCL micelles (IC50 = 75 ± 3.97 ng/mL). This was due to the higher release rate of MUC-30 from PEG-b-PLA micelles compared to PEG-b-PCL micelles. Therefore, MUC-30-loaded PEG-b-PLA micelles could be a promising candidate for breast cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Foley urinary catheters were coated by chlorhexidine‐loaded micelles and chlorhexidine‐loaded nanospheres. In our prior study, the nanocoating of Foley urinary catheter was investigated for chlorhexidine‐release study, degradation, antibacterial evaluation, and cytotoxicity assessment. These studies presented the 1 month antibacterial property of nanocoating deposited via the layers of micelles and nanospheres. In this study, we evaluated the biocompatibility of these catheters, including hemocompatibility, skin irritation, skin sensitization, and stability during the age of coated urinary catheter. Results demonstrated that coated urinary catheters presented slight hemolysis, whereas skin irritation on rabbit and skin sensitization on Dunkin Hartley guinea pig showed no signs of dermal toxicity, which indicated that inflammation, redness, and swelling did not occur. Moreover, the stability of coated urinary catheters during storage indicated no change in chlorhexidine peaks by high performance liquid chromatography. Information from these studies supports the biocompatibility of coated urinary catheters via nanocoating and their use as indwelling devices to prevent urinary tract infections. [ABSTRACT FROM AUTHOR]

Two types of chlorhexidine-loaded nanoparticles (CHX-loaded nanoparticles) were prepared: poly(ethylene glycol)-block-poly(ε-caprolactone) micelles and poly(ε-caprolactone) nanospheres. They were prepared by the solvent evaporation method and were used to coat the Foley urinary catheters. The 90 bilayers of dip coating with chlorhexidine-micelles and the 40 cycles of spray coating with chlorhexidine-nanospheres were investigated. The coating provided the CHX content as high as 93.59 ± 9.14 μg/cm2 and the thickness of coating was 9.17 ± 0.08 μm. Coated catheters were also investigated in the in vitro chlorhexidine-release, antibacterial activity, and cytotoxicity. CHX release from the coated catheters was controlled. The bacteria proliferation was inhibited up to 28 days and showed the reduction of bacteria on the coated catheter surface. Coated catheters showed no biofilm on the surface. In addition, the cytotoxicity showed no cytotoxic effect from the coating. These nanocoating systems promoted potential uses for indwelling catheter and urinary tract infection. [ABSTRACT FROM AUTHOR]

Herein, we design inflammation-responsive nanocapsules containing two antibiotics. The releases are programmed to be triggered under conditions occurring at the different stages of wound healing. The nanocapsules exhibit excellent antibacterial activities against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Incorporation of small amounts of nanocapsules in hydrogels leads to efficient antibacterial wound dressings. [ABSTRACT FROM AUTHOR]

A cyclic polymer lacks chain ends and hence cyclic polymers with molecular weights greater than the renal threshold for elimination should circulate longer than their linear-polymer counterparts when injected into animals. The studies have shown that radiolabeled cyclic polymers with molecular weights greater than the renal threshold have longer blood circulation times in mice than do linear polymers of comparable molecular weight.

The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r2*) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system. [ABSTRACT FROM AUTHOR]

In this study, chlorhexidine-loaded poly(ε-caprolactone) nanospheres (CHX-NS) were prepared and successfully coated on the urinary catheters. Properties of CHX-NS were evaluated including drug loading content and the nanosphere size. Effects of different lyoprotectants for long-term storage of CHX-NS were also investigated. In vitro release study and antibacterial activity were also conducted using 20 cycles coated-urinary catheters. Results showed that the high-pressure emulsification-solvent evaporation technique provided the drug loading content at 1.14 ± 0.16% and the size of nanospheres was 152 ± 37 nm. The suitable lyoprotectant for long-term storage of CHX-NS was sucrose which provided noticeably no aggregation at the degree of reconstitution at 89.95%. The amount of CHX loading on coated catheters was at 4.55 ± 0.31 mg. Drug release from the coated catheters in artificial urine could be prolonged up to 2 weeks and bacteria proliferation was inhibited up to 14 days. These results suggest that the antimicrobial activity of CHX-NS reduces the adherence of the uropathogens to the catheter surface. Chlorhexidine-loaded polymeric nanospheres were fabricated which can be successfully coated on urinary catheters. These systems have potential use for prolonged antimicrobial applications. [ABSTRACT FROM AUTHOR]

In this work, paclitaxel-encapsulated polymeric depots were prepared and characterized as drug delivery system for cancer chemotherapy against hepatocellular carcinoma. Effects of different parameters, including drug-loading content, polymer concentration and depot weight on depot formation, percentage of sustained-release taxol and drug release profile were evaluated. Paclitaxel-loaded depots were successfully formed at the polymer concentration above 25% w/v. For all formulations, paclitaxel could be encapsulated with very high percentage of sustained-release taxol (>90%). The release rate of paclitaxel from depots could be controlled by the amount of drug-loading content, polymer concentration and depot weight. Cytotoxicity against liver cancer cell line, HepG2, was evaluated by medium extraction method. Paclitaxel releasing from depots showed cytotoxic effect against HepG2 at different incubation times, whereas blank depots exhibited no cytotoxicity. [ABSTRACT FROM AUTHOR]

Background: Semi-synthetic andrographolide analogue (19-triphenylmethyl ether andrographolide, AG 050) is a C-19 substituted andrographolide which is the major constituent fromAndrographis PaniculataNees (Acanthaceae). The analogue has previously been reported to be highly cytotoxic against several cancer cell lines. Nevertheless, its poor water solubility limits clinical applications of this compound. Objectives: To improve the aqueous solubility and bioavailability of AG 050 by protonation and encapsulation in poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-b-PLA) polymeric micelles. Materials and methods: PEG-b-PLA micelle was employed as a nanocarrier for AG 050. The physicochemical properties andin vitrocytotoxicity against cholangiocarcinoma (CCA) (KKU-M213) cell line were done in this study. Result and discussion: Hydrochloride salt of AG 050 (AG 050-P) greatly enhanced the solubility of this compound (15-fold). PEG-b-PLA was able to encapsulate AG 050-P in hydrophobic core with a significant increase in the amount of AG 050-P in aqueous solution (280-fold). Film sonication method provided greater results in drug-loading study as compared to micelles via solvent evaporation. In addition, the encapsulated AG 050-P exhibited sustained release pattern and excellent cytotoxicity activity against KKU-M213 with IC50of 3.33 µM. Conclusion: Nanoencapsulation of AG 050-P implicated its potential development for clinical use in CCA treatment. [ABSTRACT FROM AUTHOR]