Drug release from alpha-TCP cement containing tetracycline hydrochloride (TTCH) was studied in vitro. Results from X-ray diffraction study indicated that TTCH did not prevent the hydration of alpha-TCP. In vitro drug release study showed that TTCH release could sustain over 1200 h, and the release was controlled by two mechanisms: (1) diffusion of free TTCH molecules through the porous cement (square-root-of-time kinetics); (2) dissociation of TTCH from the apatite-TTCH complex (zero-order kinetics). The mechanism controlling release would changed with the variety of the antibiotic content of cement pellets, as a result of TTCH adsorption and bonding on calcium phosphates. The first mechanism was predominantly for low concentration system TTCH-loaded apatite cement systems at the initial release period, and for high concentration TTCH-loaded apatite cement systems. As for low concentration TTCH-loaded apatite cement systems at later release stage, drug release was controlled by the coupling of the two mechanisms.
Anti-Bacterial Agents ; pharmacokinetics ; Biocompatible Materials ; Bone Cements ; Calcium Phosphates ; Diffusion ; Drug Carriers ; In Vitro Techniques ; Tetracycline ; pharmacokinetics ; X-Ray Diffraction

Cell/gene-activated biomaterials are the main tendency and characteristics of the biomaterial researches for the future. The gene delivery based on the polymeric materials as vectors has potential applications in gene therapy, regenerative medicine and tissue engineering. In this paper, the application of layer-by-layer (LBL) technique in advanced biomaterial surface engineering is reviewed and its potential application in the construction of in situ gene delivery system onto biomaterial surface is in turn addressed. These are of great significance to biomaterial researches.
Biocompatible Materials ; chemistry ; DNA ; metabolism ; pharmacokinetics ; Regenerative Medicine ; methods ; Surface Properties ; Tissue Engineering ; methods ; trends ; Tissue Scaffolds ; Transfection

Growth factors play an important role in cell adhesion and proliferation as well as in tissue regeneration. By incorporating growth factors into polymer scaffolds, controlled release of them can be performed. The release mechanism is varied with the incorporation methods. In this paper, the latest advances in the controlled release of growth factors by blending, hydrogel, microsphere embedding and chemical bonding are reviewed. The potential application of ultrafine fibric embedding in growth factor delivery is described as well.
Biocompatible Materials ; Blood Vessel Prosthesis ; Drug Delivery Systems ; methods ; Growth Substances ; pharmacokinetics ; Hydrogels ; Microspheres ; Tissue Engineering ; methods

Chitosan microsphere has been wildly researched in controlled release of protein and peptide drug because of its excellent mucoadhesive and permeation enhancing effect across the biological surfaces. The control of the size and size distribution of microspheres is necessary in order to improve reproducibility, bioavailability, and repeatable release behavior. In this work, uniform-sized chitosan microspheres containing insulin were prepared by a novel membrane emulsification technique combined with glutaraldehyde crosslinking method. In order to prepare uniform-sized chitosn microspheres, it is necessary to modify hydrophilic membrane into hydrophobicity. It is found that there exists a linear relationship between the size of chitosan microspheres and pore size of the membrane used, so it is easy to control the size of microspheres by using membranes with different pore size. In this study, the effect of different amount of crosslinker and crosslinking time on microspheres' morphology, encapsulation efficiency (EE) and release profile of drug in vitro were investigated. It is shown that the morphology of microspheres is more smooth and spherical, and the release rate is slower with the increase of amount of glutaraldehyde and prolongation of crosslinking time. When the molar ratio of amino group of chitosan to aldehyde group of glutaraldehyde is 1:0.7, and crosslinking time is 1 h, the highest EE was obtained (about 65%). Date obtained suggest that chitosan microspheres prepared by this new method would be a promising system for controlled release of protein drugs.
Biocompatible Materials ; chemistry ; Chitosan ; chemistry ; Cross-Linking Reagents ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemical synthesis ; Emulsions ; Glutaral ; chemistry ; Humans ; Insulin ; pharmacokinetics ; Microspheres ; Particle Size

OBJECTIVETo study the expression of green fluorescent protein gene and immunogenicity of ES312 vaccine both mediated by Starburst polyamidoamine (PAMAM) dendrimers in vivo.

METHODSThe complex of green fluorescent protein or ES312 gene with Starburst PAMAM dendrimers were injected intramuscularly in Balb/c mice. The expression level and distribution of green fluorescent protein gene was detected by flow cytometer, Western blot and immunofluorescence assay. The immunogenicity of DNA vaccine was detected by enzyme-linked immunosorbent assay.

RESULTSThe expression of green fluorescent protein mediated by Starburst PAMAM dendrimers was found in heart, liver, spleen, lung, kidney, brain and injected muscle from 2 hours to 7 days after the vaccination. The highest expression level of the gene was detected in kidney, as well as in endothelial cells. The antibody response evoked by the DNA vaccine carried by the Starburst PAMAM dendrimers was significantly higher than that of the net DNA vaccination. Vaccination with Starburst PAMAM dendrimers elicited higher expression level of the gene in brain and kidney than with the net gene itself.

CONCLUSIONAs a novel non-viral DNA carrier with low self-antigenicity, Starburst PAMAM dendrimers have potential to mediate DNA transfer and expression in vivo.

Animals ; Biocompatible Materials ; pharmacology ; Dendrimers ; Drug Carriers ; pharmacology ; Female ; Green Fluorescent Proteins ; genetics ; pharmacokinetics ; Malaria Vaccines ; immunology ; Mice ; Mice, Inbred BALB C ; Polyamines ; pharmacology ; Vaccination ; Vaccines, DNA ; immunology

In this paper, the pharmacokinetics of ferulic acid loaded liposome-in-chitosan-microspheres was investigated. Eighteen Sprague-Dawley rats were divided into 3 groups randomly. Each group was administered orally of ferulic acid, ferulic acid loaded chitosan microspheres and ferulic acid loaded liposome-in-chitosan-microspheres, respectively. Then blood samples were obtained from fossa orbitalis at different time points. The concentration of ferulic acid in blood was analyzed by a HPLC method using coumarin as internal standard. The data were analyzed by DAS program. The t(max), MRT and t(1/2beta) of liposome-in-chitosan-microspheres were 2.500, 7.487 and 7.818 h, respectively, which were much longer than crude drug and chitosan microspheres. This results demonstrated that liposome-in-chitosan-microspheres had better sus-tained-releasing property. The AUC of liposome-in-chitosan-microspheres was 6.08 times higher than crude drug and 1.21 times higher than chitosan microspheres, which verified that liposome-in-chitosan-microspheres could enhance oral absorption.
Absorption ; Administration, Oral ; Animals ; Anticoagulants ; administration & dosage ; blood ; pharmacokinetics ; Biocompatible Materials ; Chitosan ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Liposomes ; Male ; Microspheres ; Orbit ; blood supply ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Time Factors

As a kind of biomaterial, carboxymethyl chitosan (CMC) has excellent biodegradable and bioacceptable capabilities using. This study was aimed to probe into the feasibility of CMC to prepare the implantable sustained release Ciprofloxacin Hydrochloride (CPX) microspheres(MS), and to go further into the pharmaceutic technology, the morphology and the characteristics of in vitro release of the microspheres. First, we prepared the microspheres by emulsification and cross-linking technology. Then, scanning electron microscopy (SEM), infrared spectrum (IR) and differential thermal analysis (DTA) were used to detect the structure and morphology of the MS. The in vitro release of CPX/CMC-MS and the CPX content of the MS were detected through continuous-flow releasing system. We found that the structure and morphology of the MS were affected by the conditions of preparation such as emulsification and cross-linking temperature, ionic strength and stirring speed, that the releasing time of CPX was more than 7 days, and that the releasing behaviors of the microspheres conformed to the Higuchi model. So we drew the conclusions that CMC could be used as a kind of absorbable and implantable adjuvant for sustained release, the technology of emulsification and cross-linking was proved to be feasible, stable and simple.
Absorbable Implants ; Biocompatible Materials ; Biodegradation, Environmental ; Chitin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Chitosan ; Ciprofloxacin ; administration & dosage ; pharmacokinetics ; Cross-Linking Reagents ; Delayed-Action Preparations ; Drug Carriers ; chemical synthesis ; Humans ; Microspheres

Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism.
Biocompatible Materials/*pharmacokinetics ; Cell Line, Tumor ; Drug Delivery Systems/methods ; Endocytosis/*physiology ; Endosomes/physiology ; Humans ; Lung Neoplasms/drug therapy/*metabolism ; Macrolides/pharmacology ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Nanoparticles/*administration & dosage ; Sodium Azide/pharmacology ; Sucrose/pharmacology ; Temperature

AIMTo evaluate the effects of an array of additives on drug release from double-layered poly(lactic-co-glycolic acid) (PLGA) matrices.

METHODSAdditives differing in molecular size, hydrophilicity and steric configuration were selected for this study. An anti-proliferative 2-aminochromone, U-86983 (U-86, Pharmacia and Upjohn), was used as a model agent because of our interest in investigating local drug delivery systems for the inhibition of restenosis.

RESULTSIn vitro release of U-86 PLGA matrices without additive showed a typical biphasic release kinetics, i.e. a slow diffusion release (Phase I) followed by a fast erosion-mediated release (Phase II). The water-soluble additives in PLGA matrices changed the biphasic release pattern to a near monophasic profile by increasing the release of the Phase I. Increasing the ratio of additives to PLGA in matrices caused a significant increase in U-86 release rates. A high molecular weight water-soluble additive, Pluronic F127, resulted in a matrix showing perfect zero-order release kinetics. The morphologic evaluation of matrices using scanning electron microscopy indicated that the water-soluble additives were leachable and thus generated a highly porous structure in the matrices. Conclusion Water-solubility, molecular size and steric configuration of additives are the important determinants in generating various types of pore structures in polymer matrix which in turn affect the release mechanism and release kinetics.

Biocompatible Materials ; chemistry ; Chromones ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Excipients ; chemistry ; Lactic Acid ; chemistry ; Molecular Weight ; Morpholines ; administration & dosage ; chemistry ; Pharmacokinetics ; Poloxamer ; chemistry ; Polyglycolic Acid ; chemistry ; Polymers ; chemistry ; Tartrates ; chemistry

OBJECTIVETo investigate the role of vancomycin-loaded calcium sulphate in the treatment of osteomyelitis.

METHODSWe implanted vancomycin-loaded calcium sulphate into 24 patients with traumatic osteomyelitis who were treated in our hospital from February 2008 to February 2010,and then the antibiotic concentrations in the lesions were measured.Bacterial culture results,inflammatory markers,as well as wound healing were observed.X-ray was performed in the location where the vancomycin-loaded calcium sulphate was implanted.The blood vancomycin level as well as liver and kidney functions were determined.

RESULTSThe vancomycin concentration in the lesion exceeded the effective therapeutic concentrations and the minimum inhibitory concentration,while the blood concentration was low.The liver and renal function remained normal.The safety profile was good,and the cure rate of osteomyelitis reached 100%.

CONCLUSIONSThe vancomycin-loaded calcium sulphate can release high-concentration vancomycin in the diseased sites without causing high blood concentration.Also,it can guide the regeneration of bones.Therefore,it is effective and safe in treating osteomyelitis.

Adolescent ; Adult ; Anti-Bacterial Agents ; therapeutic use ; Biocompatible Materials ; Calcium Sulfate ; therapeutic use ; Child ; Drug Carriers ; Female ; Humans ; Male ; Middle Aged ; Osteomyelitis ; therapy ; Vancomycin ; pharmacokinetics ; therapeutic use ; Young Adult