Hydroxyapatite porous scaffold engineered with biological polymer hybrid coating for antibiotic Vancomycin release

The purpose of this study is to improve hydroxyapatite (HA) porous scaffolds via coating with biological polymer-HA hybrids for use as wound healing and tissue regeneration. Highly porous HA scaffolds, fabricated by a polyurethane foam reticulate method, were coated with hybrid coating solution, consisting of poly(-caprolactone) (PCL), HA powders, and the antibiotic Vancomycin. The PCL to HA ratio was fixed at 1.5 and the drug amounts were varied [drug/(PCL + HA) = 0.02 and 0.04]. For the purpose of comparison, bare HA scaffold without the hybrid coating layer was also loaded with Vancomycin via an immersion-adsorption method. The hybrid coating structure and morphology were observed with Fourier transformed infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The effects of the hybrid coating on the compressive mechanical properties and the in vitro drug release of the scaffolds were investigated in comparison with bare HA scaffold. The PCL-HA hybrid coating altered the scaffold pore structure slightly, resulting in thicker stems and reduced porosity. With the hybrid coating, the HA scaffold responded to an applied compressive stress more effectively without showing a brittle failure. This was attributed to the shielding and covering of the framework surface by the coating layer. The encapsulated drugs within the coated scaffold was released in a highly sustained manner as compared to the rapid release of drugs directly adsorbed on the pure HA scaffold. These findings suggest that the coated HA scaffolds expand their applicability in hard tissue regeneration and wound healing substitutes delivering bioactive molecules.     

Combined cerium oxide nanocapping and layer-by-layer coating of porous silicon containers for controlled drug release

Local drug release in close vicinity of solid tumors is a promising therapeutic approach in cancer therapy. Implantable drug delivery systems can be designed to achieve controlled and sustained drug release. In this study, ultrathin porous membranes of silicon wafer were employed as compatible drug reservoir models. An anticancer model drug, curcumin (CUR), was successfully loaded into porous silicon containers (8.94?±?0.72% w/w), and then, cerium oxide nanocapping was performed on the open pores for drug protection and release rate prolongation. Next, layer-by-layer surface coating of the drug container with anionic (alginate) and cationic (chitosan) polymers rendered pH-responsivity to the device. The drug release profile was studied using reflectometric interference Fourier transform spectroscopy at different pH conditions. It was determined that faster decomposition of the polymeric layers and subsequent CUR release occur in acidic buffer (pH 5.5) compared to a neutral buffer. Various characterization studies, including dynamic light scattering, Fourier transform infrared spectroscopy, scanning and transmission electron microscopy, contact angle measurement, ultraviolet–visible spectroscopy, and X-ray powder diffraction revealed that our system has the required physicochemical properties to serve as a novel pH-sensitive drug delivery implant for cancer therapy.     

pH-sensitive sodium alginate/calcined hydrotalcite hybrid beads for controlled release of diclofenac sodium

Objective: The aim of this study was to prepare pH-sensitive sodium alginate/calcined hydrotalcite (SA/CHT) hybrid bead with improved the burst release effect of the drug.

Materials and methods: A series of pH-sensitive SA/CHT hybrid beads were prepared by using Ca²⁺ cross-linking in the presence of diclofenac sodium (DS) and SA. The structure and drug loading of the beads were characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The swelling and the drug release of the fabricated beads were investigated by the pH of test medium and CHT content.

Result: The formed positively charged hydrotalcite layers were adsorbed on the negatively charged SA polymer chains through electrostatic interaction and act as inorganic cross-linkers in the three-dimensional network. Compared to pure SA beads, the incorporation of CHT enhanced the drug encapsulation efficiency, improved the swelling behaviors and slowed the drug release from the hybrid beads.

Discussion and conclusions: The electrostatic interaction between hydrotalcite and SA has restricted the movability of the SA polymer chains, and then slowed down swelling and dissolution rates in aqueous solutions. The results provided a simple method to moderate drug release and matrix degradation of the SA beads.     

Porous TiO2 films on Ti implants for controlled release of tetracycline-hydrochloride (TCH)

Micro- and nano-porous TiO₂ films were created on the surface of Ti implants using micro-arc oxidation and anodic titanium oxide treatments, respectively, to load a sol-gel derived silica xerogel for the controlled release of the antibiotic drug, tetracycline-hydrochloride (TCH). When the silica xerogel containing TCH was loaded into porous TiO₂ films, a very high drug loading efficiency was observed compared to when it was loaded in Ti implants without a TiO₂ film. Moreover, TCH was released in a controlled manner for up to 7 days.     

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M_c), polymer volume fraction in swollen state (V_2s), number of repeating units between crosslinks (M_r) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.     

Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Abstract

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

Water based silicone elastomer controlled release tablet film coating V - A statistical approach

The silicone elastomer latex formulated with polyethylene glycol and colloidal silica produced a controlled release film coating on potassium chloride tablets. The release rate of potassium chloride was controlled by the total amount of polyethylene glycol and the weight fraction of polyethylene glycol 8000 and 1450 incorporated in the coating. A mathematical model was developed to quantitate the effect of coating components on the drug release rate using the statistical extreme vertices design. The predictive capability of this functional relationship was tested and validated experimentally.     

Vancomycin–chitosan composite deposited on post porous hydroxyapatite coated Ti6Al4V implant for drug controlled release

Through the hydrogen bonds and the deprotonation, the vancomycin–chitosan composite has been originally deposited on Ti4Al4V by electrochemical technology. However, the rapid destruction of the hydrogen bonding between them by polar water molecules during immersion tests revealed 80% drug burst in a few hours. In this study, the post porous hydroxyapatite (HA) coated Ti4Al4V is prepared for the subsequent electrolytic deposition of vancomycin–chitosan composite to control the drug release. As expected, the initial burst is reduced to 55%, followed by a steady release about 20% from day 1 to day 5 and a slower release of the retained 25% after day 6, resulting in bacterial inhibition zone diameter of 30 mm which can last for more than a month in antibacterial tests, compared with the coated specimen without HA gradually loosing inhibition zone after 21 days. Besides, the cell culture indicates that the vancomycin–chitosan/HA composite coated has enhanced the proliferation, the differentiation and the mineralization of the osteoblast-like cell. In general, it is helpful for the osteointegration on permanent implants. Consistently, it effectively provides the prophylaxis and therapy of osteomyelitis according to the results of the rabbit infection animal model.     

Heparin-functionalized collagen matrices with controlled release of basic fibroblast growth factor

Tissue engineering scaffolds with controlled long-term release of growth factors are constructed in an attempt to mimic the intelligent ability of the extracellular matrix (ECM) to release endogenous growth factors. In this study, collagen sponges (Collagen group) were modified by N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) crosslinking (EDC/NHS group) and heparin immobilization (EDC/NHS-H group), and subsequently seeded with human umbilical vein endothelial cells (HUVECs). Native and modified sponges were pre-adsorbed with basic fibroblast growth factor (bFGF) to evaluate the sustained release and bioactive maintenance of bFGF from the sponges. We found that modified collagen matrices permitted HUVECs to proliferate and migrate well and to distribute uniformly. The EDC/NHS-H group exhibited an excellent sustained-release profile and bioactive maintenance of the pre-adsorbed bFGF as compared with the Collagen and EDC/NHS groups. These results suggest that heparin-functionalized collagen matrices can support a controlled release of bFGF and thus, have potential as a tissue engineering scaffold.     

Water based silicone elastomer controlled release tablet film coating VI: The effect of tablet shape

Abstract

The silicone elastomer latex containing colloidal silica and poloyoxyethylene glycol 8,000 was shown to produce controlled released film coating on potassium chloride tablets with different shapes. The tablet shape did not affect the zero-order release characteristic of the active ingredinent from the coated tablests. With the same coating weight, the capsule shaped tablets exhibited a faster drug release rate as compared to the oval and round deep-cup shaped tablets.     

Nanoparticle formulation for controlled release of capsaicin

Capsaicin might be an effective pharmacological agent for the treatment of discogenic back pain due to its effect on pain control neuronal degeneration. Therefore, capsaicin-loaded nano- and micro-particles for sustained release were formulated by nano-precipitation or oil-in-water single emulsion solvent evaporation/extraction method. First, the capsaicin-loaded PLGA nanoparticles were prepared by nano-precipitation method. By increasing the volume of oil-water ratio from 1:2 to 1:5, slight changes in size from 162 +/- 3 nm to 153 +/- 3 nm and in drug loading efficiency from 25% to 20% were observed, whereas the drug release period was significantly changed from 11 days for 1:2 to 5 days for 1:5 ratio. To get a more sustained release, a modified single emulsion method was applied with three kinds of biocompatible polymers (PLLA, PLGA, and PCL). Among them, PLLA particles showed a much sustained release profile than PLGA or PCL ones with the similar size. For PLLA particles, particles size and drug encapsulation efficiency increased as the oil/water ratio decreased, and the bigger particles showed the slower release profiles as well as the higher drug-loading efficiency, thus about 1 month release was obtained with 800 nm particles. In conclusion, formulation for the controlled release of capsaicin from 1 week to 1 month was prepared by using biocompatible nanoparticles.     

Water based silicone elastomer controlled release tablet film coating VI: The effect of tablet shape

The silicone elastomer latex containing colloidal silica and poloyoxyethylene glycol 8,000 was shown to produce controlled released film coating on potassium chloride tablets with different shapes. The tablet shape did not affect the zero-order release characteristic of the active ingredinent from the coated tablests. With the same coating weight, the capsule shaped tablets exhibited a faster drug release rate as compared to the oval and round deep-cup shaped tablets.     

Polymersome-loaded capsules for controlled release of DNA

The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.     

A novel Ti cored wire developed for wire-feed arc deposition of TiB/Ti composite coating

A novel Ti cored wire containing TiB2,Al60V40 and Ti6Al4V mixed powders was developed for wire-feed arc deposition of TiB/Ti composite coating,to enhance the hardness and wear resistance of Ti alloy.Results showed that after experiencing several chemical reactions,the wire was melted in the arc zone and turned into nonuniform droplets composed of Ti-Al-V-B melt and undecomposed TiB2 particles.With the increase of welding current,the detachment time of droplet shortened while the transfer frequency accelerated,accompanied by the improvement in coating surface quality.The spatial distribution of TiB whiskers in coating was governed by welding current.A uniform distribution could be achieved as welding current was sufficient at the expense of elevated dilution ratio,while increasing wire feeding speed could compensate the dilution loss of TiB whisker to some extent.The decomposition process of TiB2 particles and the microstructure evolution mechanism of coating was discussed in detail.The optimum coating possessed uniform microstructure,relatively low dilution ratio,and high hardness(639.1 HV0.5)as compared with Ti6Al4V substrate(326 HV0.5).Indentation morphology analysis verified the excellent performance was ascribed to the load-sharing strengthening of TiB whiskers.This study provides a high-efficiency fabrication method for the ever-developing titanium matrix composites(TMCs)coating.