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In this research, the effect of layer-by-layer (spray and dip) coating followed by annealing of vancomycin (VCM) and poly(ε-caprolactone) nanospheres (PCLnp) on Schanz pins for prolonged antibacterial activity was investigated. Nanospheres were prepared using the high-pressure homogenizer method and characterized by both functional groups and particle size. The in vitrorelease profile revealed that after 28 days, the cumulative release of VCM from the VCM-PCLnp coated pins was 753.68 ± 0.19 μg. The coated pins released VCM at a concentration greater than the minimum inhibitory concentration (MIC) and sustained this release for 28 days. Irritation, hemolysis, sensitization, and cytotoxicity assays confirmed that VCM-PCLnp coated pins were highly biocompatible. Additionally, antibacterial assays against methicillin-resistant Staphylococcus aureus(MRSA) revealed prolonged antibacterial resistance. Specifically, the assays demonstrated effective inhibition of Staphylococcus aureus (S. aureus),including the methicillin-resistant strain. This approach involves coating the implants with antibiotics and polymeric nanospheres using a layer-by-layer (dip and spray) method to prolong their antibacterial activity. The results of this study show great promise for successfully treating implant-associated infections. Consequently, we recommend this method for coating other medical devices.

Silica nanocapsules (SiO2NCs) are usually prepared with cationic surfactants that are not cytocompatible. Dialysis can be used to remove surfactants but leads to instability of the SiO2NCs when they are in the presence of proteins or biological media. Herein, SiO2NCs stabilized with a reactive surfactant are synthesized to prevent leaching upon dialysis. The SiO2NCs show superior stability and biocompatibility compared with SiO2NCs prepared with conventional surfactants. The SiO2NCs can be used in self-healing materials, smart agriculture and biomedical applications.

The focus of current study was to evaluate the in vitroand in vivobiocompatibility of nano-coated orthopedic bone plate. In our previous work this nano-coating was designed, characterized and its antibacterial properties and cell toxicity were assessed. This new strategy of nano-coating designed with antibacterial niosomes, were coated on orthopedic bone plate via layer-by-layer deposition. Therefore in the present study it was of paramount importance to measure its biosafety before it can be further evaluated for clinical studies. Fibroblast morphology, proliferation and cell adhesion properties were examined. The results demonstrated that coated bone plate exhibited no adverse effects and enhanced cell adhesion and proliferation than the uncoated bone plate. The extracts from the coated bone plate were tested against human blood cells and demonstrated excellent hemocompatibility. In vivoskin toxicities such as skin sensitization and irritation were investigated on guinea pigs and rabbits, which revealed no toxicity or any signs of inflammation and suggested its superior biocompatibility. The data gathered from these studies are promising and proposed that these antibacterial nano-coatings are non-toxic and has potential to utilize in various implant coating applications.

Chlorhexidine-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) micelles (CHX-micelles) were prepared by the solvent evaporation method and were used to coat urinary catheters. The layer-by-layer (LbL) dip coating technique was used to coat the micelles onto the catheters, which consisted of the alternation of coating with CHX-micelles and poly(acrylic acid). The number of LbL nanocoating cycles was varied, and the properties of the coated catheters were investigated for their drug content and the coating thickness. The optimal coated catheter had 90 bilayers, which provided the maximum CHX content at 32.3 ± 1.4 μg/cm2, and the thickness of the thin film on these coated catheters was 6.87 ± 0.36 μm. Coated catheters were studied in the in vitroCHX-release, antibacterial activity, cytotoxicity, and hemolytic activity. Drug release from the coated catheters was controlled, and bacteria proliferation was inhibited for up to 6 days. Results suggest that the antimicrobial activity of the coated catheter reduces the adherence of uropathogens to the catheter's surface. The cytotoxicity and hemolytic activity of the coated catheters showed biocompatible properties. The coated catheter presented the potential to inhibit uropathogen colonization and formation. This nanocoating technology can also be applied to other medical implants that carry the risk of infection.

In this study, glucose-targeted and glucose-free micelles composed of a diblock copolymer of poly(ethylene glycol)-b-poly(lactide) that encapsulated superparamagnetic iron oxide (SPIO) and doxorubicin (DOX) in their hydrophobic core were fabricated. Glucose micelles showed 5.01 ± 0.3% drug loading content and 103 ± 4.0 nm size. We also endeavoured to observe the cellular uptake of these targeted and non-targeted micelles. The anticancer efficacy of the targeted, non-targeted micelles and free doxorubicin at the equivalent dose of 32 mg/kg were evaluated on the nude mice bearing tumours. Glucose micelles exhibited significant anticancer effects than free doxorubicin and non-targeted micelles. It was noteworthy that free doxorubicin showed toxicity at the site of injection. H&E staining of targeted micelles demonstrated remarkable changes in tumour architecture, also exerted higher percentage of necrosis (82.5%). Prussian blue staining revealed that tumour tissues with glucose DOX/SPIO micelles displayed much higher iron density than the non-targeted micelles, which could be employed for imaging tumour growth in the future. The data revealed that glucose targeted therapy can inhibit hepatocellular carcinoma when compared to non-targeted micelles. These specialised targeted micelles can serve as a theranostic agent hence, suggesting a useful targeted therapeutic and imaging strategy against liver cancer.

Hepatocyte encapsulation serves as an alternative solution for prolonging the hepatic pre-transplantation period in acute liver disease patients. The basic fibroblast growth factor (bFGF) was introduced and optimized to enhance hepatocyte viability and regeneration at 1 ng/ml concentrations. The bFGF was preserved with double-emulsion PLGA microspheres to release over a period of time sustainably. Different techniques were used to calculate the percentages of loading content, encapsulation efficiency, and release profile. In addition, the bFGF-loaded microspheres were measured to be 1.8226 ± 0.7176 μm in size and illustrated smooth surface morphology. Herein, the immortalized hepatocyte-like cell line (imHC) and bFGF-loaded PLGA microspheres were encapsulated inside the alginate microbeads using the electrostatic extrusion method. Under the scanning electron microscope, the bead morphology was observed to have a smooth surface, and the estimated size was 758 ± 32.9 μm. Moreover, the confocal images showed the evenly distributed cells inside the microbeads in a 3D structure. Over a 14-day observation, the microsphere exhibited significant effects on imHC viability. Therefore, it can be concluded that the co-encapsulation of bFGF-loaded microspheres and imHCs inside alginate microbeads (bFGF-HB) has presented itself as a promising approach to enhance the cell survivability of encapsulated cells.

Bacterial infection in Schanz pins is a major problem in orthopedic surgery. Infection is mostly caused by gram-positive bacteria including Staphylococcus aureusand Staphylococcus epidermidis. In this study, vancomycin and poly (lactic acid) were chosen as an antibacterial agent and polymer matrix, respectively for the antibacterial coating on Schanz pins. Schanz pins were dip-coated and the release profile of vancomycin from the coating in the PBS at pH 7.4 was evaluated. The degradation of the coating in PBS at pH 7.4 was observed by scanning electron microscope. The concentration of vancomycin released from the coating was higher than the MIC level of Staphylococcus aureus(ATCC 25923) for at least 44 days. Scanning electron microscope showed that the coating was degraded gradually in PBS. The outer surface of the coating showed much faster degradation than that of the inner surface. The antibacterial activity was tested against Staphylococcus aureus(ATCC 25923). Results show that vancomycin release from the coating was able to provide the growth inhibition of Staphylococcus aureusup to 1 month. These results demonstrate that the surface coating of vancomycin and poly (lactic acid) was successful in inhibiting the growth of gram-positive bacteria on Schanz pins.

The control of initial burst release of drugs from polymeric depots is a promising approach to achieve the dose level of therapeutic agents after administration. This study describes the method to control initial burst release of doxorubicin (Dox) from injectable polymeric depots made from PLGA 70:30, by modifying the weight ratio between protonated and deprotonated Dox that were incorporated into the depots. High initial burst release within 24 h was found at 86.6 ± 5.3% in depots incorporating with 100% protonated Dox. Burst release values were dramatically reduced to 48.5 ± 2.5, 41.8 ± 1.5, 35.1 ± 2.4, 27.3 ± 2.9, and 22.0 ± 2.1% when protonated Dox ratio was reduced to 98.75, 97.5, 95, 90, and 85%, respectively. To investigate the released Dox activity, cell viability of human hepatocellular carcinoma cells (HepG2) treated with extracted medium from 100 to 85% protonated Dox-loaded depots were 5.81 ± 1.11% and 7.44 ± 0.72%. Results show that the high burst release was reduced when deprotonated Dox was used. SEM confirmed the mechanism of Dox release from PLGA depots. The incorporation of deprotonated Dox could be a promising method in controlling drug release from polymeric depots for cancer treatment in the future.

Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) imaging are combined to diagnose cancer with high physiological, anatomical, and metabolism sensitivity. For targeting hepatoma carcinoma, a drug delivery system is employed to carry drugs or chemicals to a specific area. Galactose is one of the sugar molecules which can be bound and increase uptake with asialoglycoprotein receptor (ASGP-R). In this study, superparamagnetic iron oxide nanoparticles (SPIONs), Galactose-functionalized poly(ethylene glycol)-block-poly(lactic acid) (Gal-PEG-b-PLA) and Diethylenetriaminepentaacetic acid-functionalized poly(ethylene glycol)-block-poly(lactic acid) (DTPA-PEG-b-PLA) were successfully synthesized and constructed to DTPA/Gal/SPIO micelles (targeting micelles) and DTPA/Met/SPIO micelles (non-targeting micelles). Technetium-99 m (99mTc) formed a complex with DTPA on the micelles as 99mTc/Gal/SPIO micelles by using stannous chloride and the pH was adjusted to acidic condition. The sizes of DTPA/Gal/SPIO micelles and DTPA/Met/SPIO micelles were lower than 100 nm with a spherical shape. In vitrostudy with HepG2-and L929-incubated micelles showed the intensity of blue staining of Prussian blue related to the amount of SPIO. 99mTc/Gal/SPIO micelles incubated with HepG2 exhibited signal intensity (SPECT signal) and relative R2* (MRI signal) higher than 99mTc/Met/SPIO micelles at the same time. According to these results, 99mTc-labeled Galactose-functionalized SPIO micelles have the potential for specific targeting to HepG2 and can aid in the diagnosis of cancer with MRI and SPECT dual imaging.

Delignified sugarcane bagasse (SCB) by solvent extraction was carried out at moderate condition (90°C, 4 h) in the presence of acid catalyst. To investigate the dissolution of lignin into solvent, different solvents were utilized during lignin extraction process. Delignified SCB was further hydrolyzed by cell wall degrading enzyme complexes prior to sugar determination. The results showed that n-butanol was the most promising solvent enhancing lignin dissolution which in turn led to highest yield of glucose (63.1% based on treated SCB) and no xylose was detected in hydrolysate. The lignin extraction by n-butanol in the presence of H2SO4 and subsequent saccharification process were then scaled up for lactic acid production. The maximum lactic acid was obtained at 25.7 ± 0.2 g/l from L. casei fermentation after 96 hours when sugarcane bagasse hydrolysate containing 25.6±1.4 g/l initial glucose concentration was used as substrate.

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Purpose.To explore the use of cyclodextrins (CD) to form inclusion complexes with β-lapachone (β-lap) to overcome solubility and bioavailability problems previously noted with this drug. Methods.Inclusion complexes between β-lap and four cyclodextrins (α-, β-, γ-, and HPβ-CD) in aqueous solution were investigated by phase solubility studies, fluorescence, and 1H-NMR spectroscopy. Biologic activity and bioavailability of β-lap inclusion complexes were investigated by in vitrocytotoxicity studies with MCF-7 cells and by in vivolethality studies with C57Blk/6 mice (18-20 g). Results.Phase solubility studies showed that β-lap solubility increased in a linear fashion as a function of α-, β-, or HPβ-CD concentrations but not γ-CD. Maximum solubility of β-lap was achieved at 16.0 mg/ml or 66.0 mM with HPβ-CD. Fluorescence and 1H-NMR spectroscopy proved the formation of 1:1 inclusion complexes between β-CD and HPβ-CD with β-lap. Cytotoxicity assays with MCF-7 cells showed similar biologic activities of β-lap in β-CD or HPβ-CD inclusion complexes (TD50= 2.1 μM). Animal studies in mice showed that the LD50value of β-lap in an HPβ-CD inclusion complex is between 50 and 60 mg/kg. Conclusions.Complexation of β-lap with HPβ-CD offers a major improvement in drug solubility and bioavailability.

This article describes the design and development of a novel membraneencased polymer millirod for the sustained release of an anticancer drug, 5fluorouracil 5FU. The millirod consists of two functional compartments: 1 an inner 5FUloaded monolithic millirod as the drug depot, and 2 an outer NaClimpregnated polymer membrane to control the release rate of 5FU. The inner millirod is fabricated by a compressionheat molding procedure to permit the entrapment of 5FU particles in the polyD,Llactidecoglycolide PLGA matrix. The drug loading density is controlled at 30 ww to achieve a burst release of 5FU >90 of the drug are released within 48 h from the monolithic millirod. The NaClimpregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membraneencased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5FU. Under the experimental conditions in this study, sustained release of 5FU rates between 0.1 and 0.4 mgday · cm of millirod is achieved for 2 to 5 weeks in phosphatebuffered saline pH 7.4 at 37°C. Results from this study demonstrate that membraneencased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 203–211, 2002

In this study, variation of coating parameters was performed to determine a suitable condition for a vancomycin-coated Schanz pins in poly(lactic acid) (PLA) for prolonged antibacterial activity. Herein, the solvent used to dissolve the polymer (DCM vs. CHCl3), the concentration of the polymer in the solvent (2 vs. 5% w/v), the vertical withdrawing speed of the implant from the solution (0.4 vs. 2.4 cm/s), and the number of dip-coating cycles denoted in layers (1 L vs. 3 L) were investigated for its drug loading. Results showed that the optimal parameters were at 2% w/v PLA in DCM at 0.4 cm/s withdrawing speed and at 3 cycles for a high vancomycin loading with low deviation in result. Another experiment was performed by varying the concentration (1, 2, 4% w/v) and number of dip-coating cycles (10 L, 20 L, 30 L) which finalized 2% w/v PLA at 10 cycles as the optimal drug loading at 2.04 ± 0.09 mg. When observing the drug-release profile, the prior formulation released 2.21 ± 0.01 mg or 92.88 ± 0.44% of drug in one week. To reduce the amount of drug release in the first week, the method was further improved by spray-coating with PLA nanospheres (PLA-NS) for multiple cycles (10-, 20-, and 30-NS) to prolong drug release. After one, two, and three weeks, the drug-release were around 76%, 80%, and 88%, respectively. However, more drugs were lost as the number of cycles increases which suggests that lower (10-NS) coating cycle is better. Therefore, the final process was selected to be 2% PLA dip-coated for 10 cycles then spray-coated with PLA nanosphere for 10 cycles. Results showed that this method can help prolong release for at least 24 days. A short-term bacterial and cytotoxicity tests were done for 3 days with no S.aureusformed nor cytotoxicity. These results supported that the coating was successful in inhibiting the growth of S.aureus.

This article describes the design and characterizations of coated implants for stimulating bone regeneration. To achieve successful dental implantation, there are many advances in materials, techniques, and implant design. However, long-term outcomes of osseointegration are considered to be the major factors leading to implant failure. The main potential factors causing early and late implant failures are poor bone quality and bone quantity. In an attempt to increase the success rate of implants, this work coated the surface of implants to increase osteoblast cell attachment. It is known that bone morphogenetic protein-2 (BMP-2) promote osteoblastic cells adhesion. To confirm the osseointegration, the aim of this study was to develop BMP-2 immobilization on titanium (Ti) modified by layer-by-layer technique (LBL). Firstly, the Ti surface was first modified with surface plasma treatment. Secondly, layer-by-layer nanocoating of BMP-2 on dental implant (BMP-2/Ti) and then sprayed with poly(lactide-co-glycolide) (PLGA/BMP-2/Ti). Regarding preparation of modified Ti, Ti was alternatively coated with 15 cycles of BMP-2 and sprayed with 10 cycles of PLGA. The number of layers between BMP-2 and PLGA was 15/10, 30/20, 45/30, 60/40,75/50, 90/60, and 105/70. The result of this study showed that the ratio of 75/50, 90/60, and 105/70 was suitable for BMP-2 coating. Entrapment of BMP-2 of 75/50, 90/60, and 105/70 were 6.94 ± 0.55, 7.07 ± 0.53, and 7.12 ± 0.50 μg, respectively. The coating also possessed homogeneity and good biocompatibility. Moreover, all of these coatings promoted osteoblast cell proliferation and had good stability.

Bed sheet is one of the most frequently contaminated medical equipment in the hospital. In this study, an antibacterial poly(vinyl chloride) (PVC) bed sheet coated with zinc oxide nanoparticle (ZnO-NP) was developed using multiple-layer coating technique on a large scale (1 m x 1 m). A number of coating cycles was varied, and the properties of the coated bed sheet were observed for their ZnO concentration. Coated bed sheet was also investigated for its wetting property as well as its antibacterial activity against S. aureus, S. epidermidis, E. coli, and P. aeruginosa. Results showed that bed sheet with 15 cycles of coating had the highest ZnO concentration of 0.17 mg/cm3and the highest hydrophobicity with the contact angle at 117 o± 0.76. The antibacterial activities and observation under SEM suggested that the coated bed sheet reduced the adherence of both gram-positive and gram-negative bacteria, with ZnO-NP effectiveness being higher on gram-positive compared to gram-negative bacteria. This nanocoating procedure can also be applied to other medical devices that are potentially listed as sources of infection.

Peri-implant diseases are mostly caused by a bacterial infection which leads to inflammation and bone loss at and around the implant. In this study, minocycline-loaded niosomes prepared by thin-film hydration method were coated on the dental implant for antibacterial application. Minocycline-loaded-niosomes were characterized for drug loading content, encapsulation efficiency and yield. Result demonstrated that the optimum formulation was 3:1 comprising of span 60 and cholesterol which provided the most drug loading content and encapsulation efficiency. The optimum coating cycles were 120 which could coat the highest content of drug on coated dental implants. In vitrodrug release from the coated implants was studied. Antibacterial activity and cytotoxicity of the coated implant were also investigated. Results suggested that minocycline-release from the coated dental implant could be controlled for up to 7 days which was a crucial period after implantation. During this time, inhibition of Porphylomonas gingivaliswas also noticed. In vitrocytotoxicity study revealed that the coated implant was non-toxic to osteoblast cells. Hence, results suggest that this coating strategy can be used for antibacterial coating of medical devices.

Schanz pins are orthopedic implants that are used for the fixation of external fractures. Long-term use of Schanz pins may cause infection, bacterial adhesion, and biofilm formation, and it can also lead to implant rejection. The spray coating or dip coating of an antibiotic directly onto the surface of the implants prior to use is limited to the rapid release of antibiotic for only a short time. To overcome this problem, nanospheres, which are a type of drug-delivery system, were used to control the release of antibiotics. In this research, vancomycin and gentamicin were loaded separately in Poly(lactide-co-glycolide) (PLGA) nanospheres. Nanospheres were prepared by the double-emulsion solvent evaporation method and spray-coated onto the pins. These nanospheres were characterized in terms of size, zeta potential, drug loading, and encapsulation efficiency. The release profiles of antibiotic-loaded nanospheres were determined before investigating the in vitrorelease of antibiotics from the nanosphere-coated pins. Vancomycin-loaded PLGA nanospheres (VCM-NPs) and gentamicin-loaded PLGA nanospheres (GM-NPs) indicated slightly negative charges, and the sizes were 214.70 and 499.30 nm in diameter, respectively. VCM-NPs and GM-NPs displayed drug-loading contents of 7.12% and 7.97%, respectively. The concentration of vancomycin and gentamicin released from the coated pins were higher than the minimum inhibitory concentration of Staphylococcus aureusATCC 25423 and Escherichia coliATCC 25922 which could be sustained release for 42 and 49 days, respectively. The coated pins demonstrated superior biocompatibility and long-term antibacterial activity. Furthermore, the strategy utilizes dual antibiotic coating onto the implants via loading in polymeric nanospheres for enhanced antibacterial activity. The data gathered from this study is promising and is capable of combating implant associated infections. Hence, we suggest the use of this strategy for coating other medical devices.