Controlled hydrothermal synthesis of strontium-substituted hydroxyapatite nanorods and their application as a drug carrier for proteins

Without the addition of any organic additives, both undoped hydroxyapatite (HAp) and different strontium (Sr)-substituted hydroxyapatite (SrHAp) samples with amounts from 1 to 20?mol.% were synthesized via hydrothermal route. The crystal texture, chemical functional group and microstructure were well characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and inductively coupled plasma (ICP), respectively. And the protein adsorption and release properties of bovine serum albumin (BSA) and lysozyme (LYS) were investigated on the samples to search for a well protein drug delivery vehicle. The results revealed that the pure HAp consisted of uniform nanobelts and all SrHAp samples had a rod-like morphology. The lattice parameters of SrHAp were larger than HAp, while they had similar crystal structure. The protein adsorption and release tests indicated that the incorporation of Sr into HAp lattice could increase the amounts of BSA and LYS adsorption. The BSA adsorption capacity of 1SrHAp was found to be 55.52?mg/g, which was about 14.64% higher than that of HAp. The 15SrHAp possessed the highest LYS loading amount of 90.54?mg/g, which was about three times that of HAp. And SrHAp exhibited sustained protein release capability.     

Intrinsic effect of anionic surfactant on the morphology of hydroxyapatite nanoparticles and its structural and biological properties

This paper describes the potential effect of anionic surfactant on the morphology of hydroxyapatite (HA) nanostructures during hydrothermal synthesis. Sodium dodecyl sulfate (SDS) was used as an anionic surfactant. Various concentrations of SDS were used to study morphological changes in HA due to the presence of the surfactant. The final morphology, after treatment by a hydrothermal method, revealed that the anionic surfactant induced growth in one direction (a-axis) and inhibited growth in the other (c-axis) based on the charge distribution on the crystal faces of HA. Further structural analysis (by X-ray diffraction) confirmed this growth along the a-axis. In-vitro cellular analysis revealed that the plate-like nanoparticles possess better bioactivity than their bulk counterparts. Therefore, HA nanoplates could be used for applications that include controlled drug delivery and bone mineralization.     

Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady compared to that of the un-encapsulated microspheres. In conclusion, PLGA encapsulated HAP-MSs may be a potential vehicle for the sustained delivery of Doxy.     

Enhanced bioactivity and biocompatibility of nanostructured hydroxyapatite coating by hydrothermal annealing

The crystallinity of hydroxyapatite (HA) coatings prepared by aerosol deposition may be increased by heating in air or low-temperature hydrothermal processing. From the X-ray diffraction and Fourier transform infrared spectroscopy results, it was revealed that the crystallinity of the HA coatings significantly increased after the post-annealing. Transmission electron microscopy showed that the conventional furnace heating induced the substantial growth of the HA crystallites, whereas the hydrothermal treatment did not bring about any remarkable change in the HA crystallite size, which remained below 20 nm. The bioactivity of the HA coatings was estimated by the acellular simulated body fluid immersion test. After immersion for 7 days, newly-precipitated apatite crystals were only observed on the surfaces of the samples hydrothermally treated at 170 and 190 °C. In addition, the alkaline phosphatase activity of MC3T3-E1 preosteoblast cells cultured on the hydrothermally treated samples was significantly higher than those on the as-deposited coating and conventional furnace heated samples. The enhanced bioactivity and excellent biological in vitro cellular response of the hydrothermally treated samples were attributed to their nanostructured nature and high degree of crystallinity.     

In vitro evaluation of hydroxyapatite reinforced polyhydroxybutyrate composite

Particulate hydroxyapatite (HA) was incorporated into polyhydroxybutyrate (PHB) to form a bioactive and biodegradable composite for applications in hard tissue replacement and regeneration. HA/PHB composite containing 10, 20, and 30 vol.% of HA was made for in vitro evaluation. In vitro studies were conducted using an acellular simulated body fluid (SBF). Composite specimens were immersed in SBF at 37 °C for various periods of time prior to surface analysis and mechanical testing. Results obtained from scanning electron microscopic (SEM) examination, thin film X-ray diffraction (TF-XRD) analysis, and Fourier transform infrared (FTIR) spectroscopy showed that a layer of bone-like apatite formed within a short period on HA/PHB composite after its immersion in SBF, demonstrating high in vitro bioactivity of the composite. The bioactivity and mechanical properties of the composite could be changed by varying the amount of HA in the composite. Dynamic mechanical analysis (DMA) revealed that the storage modulus (E′) of HA/PHB composite increased initially with immersion time in SBF, due to apatite formation on composite surface and decreased after prolonged immersion in SBF, indicating degradation of the composite in a simulated body environment. HA/PHB composite thus has the potential for its intended applications.     

Direct growth of carbon nanotubes on hydroxyapatite using MPECVD

For the first time carbon nanotubes (CNTs) have been successfully grown directly on hydroxyapatite (HA) by using microwave plasma enhanced chemical vapor deposition (MPECVD). Such integration has potential to capitalize on the merits of both HA and CNTs. This type of coating could be useful to improve the interface between bone and the implant. Scanning electron microscope SEM investigations show that; the surface of the CNTs is relatively clean and free of amorphous carbon. The CNTs diameters lie in the range 30-70 nm. In addition HA encapsulation by carbon was observed at a growth temperature 750 °C. Raman spectroscopy indicates that the CNTs are of high quality and the I_G/I_D ratio lies between 1.243 and 1.774. The changes in the X-ray diffraction (XRD) patterns give an indication that during the plasma deposition the HA-substrate surface is subjected to a temperature sufficient for partial conversion to the β-tricalcium phosphate via dehydroxylation.     

掺锶羟磷灰石固溶体含锶量对骨组织融合能力的影响

评价不同掺锶量羟磷灰石固溶体材料锶含量与生物降解性和骨组织融合能力之间的影响关系.5组掺锶羟磷灰石固溶体材料锶克分子含量分别取0%,1%,5%,10%和100%,烧结体植入部位为家兔胫骨;手术后分不同时段处死动物,通过四环素荧光标记和电镜扫描方法考察植入材料与骨组织界面的生物反应状况.实验结果表明5组试样材料都显示了良好的组织相容性和骨结合性,其中锶含量为5%组和10%组试样显示较强的骨引导作用,呈现出很明亮的四环素荧光带以及明显的降解现象.这说明在羟磷灰石晶体中掺入适量的锶元素可以明显改善材料的生物相容性、骨引导性、生物降解性以及骨融合性;掺锶羟磷灰石固溶体不仅可以增强新骨的生成能力,而且可以延长新骨的生成时间和增加新骨的生成量.     

锶磷灰石多孔陶瓷动物体内降解的实验研究

采用溶液反应方法制备含5%(原子分数)锶的羟磷灰石(Sr-HA)原料,经干压成型、烧结后制得孔隙率约35%的圆片状多孔体,植入新西兰大白兔脊柱两侧背脊肌中,以纯羟磷灰石试样作为实验对照;通过扫描电镜、四环素荧光标记法观察种植体试样表面生物降解性和与周围软组织之间界面状况以及四环素荧光分布,评价锶磷灰石多孔陶瓷在动物软组织内的生物降解性、对组织生长的引导性等生物学行为。结果显示,锶磷灰石种植试样3个月时表面可见由于晶体降解而呈现出大量凹陷结构,凹陷结构的边缘较中心点的降解更为明显和快速;6个月时可观察到凹陷样结构处外围有明显的从外向内吸收特征,并且可观察到大量的强亮色条索状、团状荧光带,连成一片。而羟磷灰石对照组材料表面仅见少量的降解,四环素荧光呈点状弥散样,荧光强度较低。说明锶磷灰石具有良好的组织亲和性和组织引导性;与羟磷灰石相比,锶磷灰石的降解速度快,降解程度高。锶磷灰石可能具有诱导骨基质形成的作用。     

Sol–gel synthesis and spectrometric structural evaluation of strontium substituted hydroxyapatite

Investigations of the electronic structures of substituted strontium apatites were carried out by using X-ray photo electron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction technique (XRD) has been used to determine the structural parameters. Electron microprobe microanalysis technique was used to estimate the elemental concentrations in each substituted apatite material. The present work aims at studying the changes in the electronic structure of Sr₅(PO₄)₃OH (Sr-HAP) upon isomorphic substitution by F and Cl at the OH site of apatite and Sr by Na at trans Sr-HAP. The ion exchange between Na⁺ in sodium alginate and aqueous Ca²⁺ was important for the preparation of calcium hydroxyapatite. In contrast, the reaction of sodium alginate with the mixture of Na₄P₂O₇ and aqueous Sr²⁺ afforded strontium hydroxyapatite at the specific ratio. The structure of calcium and strontium phosphates prepared from the sol–gel process evidently depended on the amount of sodium alginate introduced into the mixture of Na₄P₂O₇ and the corresponding divalent cations. The findings have ensured that substitution of Sr-HAP by Na enhances the binding energy of O and Sr core levels. It was also noticed that the same substitution decreases the binding energy of P 2s-level. These observations point out to a decrease in the electron density at P and an increase in the electron density at O in Sr atoms.     

Ionic liquid-assisted synthesis of silica particles and their application in drug release

Hollow and porous silica particles have been successfully prepared by a simple acid gelation route using the sodium silicate as the reactant in ionic liquid solution, 1-butyl-3-methylimidazolium tetrafluoroborate. The drug release behavior of the as-prepared porous silica particles is studied to reveal their potential use in drug delivery system. The current work for the synthesis of silica particles with the sodium silicate as the reactant in an ionic liquid might open new directions and opportunities to explore the application of ionic liquid in materials fields combining with the biomedical area.     

Preparation of chitosan–sodium alginate microcapsules containing ZnS nanoparticles and its effect on the drug release

Chitosan–sodium alginate microcapsules were prepared in the presence of ZnS nanoparticles via the W/O/W emulsification solvent-evaporation method. Microscopy showed that the microsphere was about 150 nm and by the absorption spectra, ZnS nanoparticles incorporated was 4 nm. Aspirin was chosen to investigate the effect of microcapsules on the drug release. It reveals that comparing with the microsphere without nanoparticles, the release speed of microsphere containing ZnS nanoparticles is significantly decreased from complete release at 10 h to 50% release by 50 h. The data of release kinetics for the microcapsules can be well fitted by the classic Higuchi model.     

Evaluation of mathematical models describing drug release from estradiol transdermal systems

The in vitro release profiles of 13 patches of estradiol (from five marketed products) were determined by the paddle-over-disk method. The transdermal systems were membrane-controlled type or matrix diffusion-controlled type. The estradiol content of test aliquots of the dissolution medium was determined by HPLC. To analyze the release mechanism, several release models were tested such as zero order, first order, Higuchi, Weibull, Korsmeyer-Peppas, and Makoid-Banakar. The release profiles showed that the drug was released at a constant rate for three patches. The drug-release rate from the other 10 patches was not constant, and diminished with the square-root of time (Higuchi model).     

Controlled drug release using nanoporous anodic aluminum oxide on stent

Local drug delivery system was demonstrated by using drug-eluting stents coated with nanoporous anodic aluminum oxide (AAO) for controlled drug release. 316 stainless steel coronary stents were coated with nanoporous AAO, which was fabricated by anodization of Al deposited on stents. Effects of diameter and depth of AAO on the release of drug were investigated. Image of the AAO pore diameter and depth were examined by SEM. Amount of the drug release from the AAO with various pore diameters and depths was analyzed by HPLC.     

Investigation of charge effects on drug release behavior for ionic thermosensitive hydrogels

The influence of various drugs with different charges on the drug release behavior in porous ionic thermosensitive hydrogels was investigated. The present hydrogels were prepared from N-isopropylacrylamide (NIPAAm) and cationic monomer, trimethyl (acrylamido propyl) ammonium iodide (TMAAI), or anionic monomer, acrylic acid (AA), or zwitterionic monomer, N′,N′-dimethyl (acrylamido propyl) ammonium propane sulfonate (DMAAPS), or nonionic monomer, poly(ethylene glycol) methylether acrylate (PEGMEA), and pore-forming agent, poly(ethylene glycol) (PEG) with different molecular weights. Caffeine as a nonionic drug, crystal violet (CV) as a cationic drug solute, and phenol red as an anionic drug solute were chosen as model drugs to perform the drug release experiment. Results show that the release ratio of caffeine in the hydrogels is not affected by the ionicity of hydrogels. The CV strongly interacted with the anionic hydrogel; thus, the CV release ratio is very low. CV is only adsorbed on the skin layer of the cationic hydrogel due to charge repulsion and is released rapidly. The result of phenol red (anionic solute) release in the hydrogels is contrary to CV. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated.     

Photo-induced formation of hydroxyapatite on TiO2 synthesized by a chemical–hydrothermal treatment

The formation of hydroxyapatite (HAp) on TiO₂ surfaces under continuous ultraviolet (UV) irradiation was investigated. Pure Ti substrates were chemically treated with H₂O₂/HNO₃ at 353 K for 20 min to form a TiO₂ gel layer. The specimens were then hydrothermally treated with an aqueous NH₃ solution in an autoclave at 453 K for 12 h. An adhesive and sufficiently crystallized anatase-type TiO₂ film could be synthesized on the Ti surface. The specimens were immersed in simulated body fluid in darkness or under UV irradiation with a centered wavelength of λ = 365 nm. Under dark conditions, a thin homogeneous HAp film was formed, with just a few spherical clusters of HAp. The UV illumination promoted the formation of HAp clusters, which may be due to the generation of functional Ti–OH or Ti–O groups on the TiO₂ surface. On the other hand, the UV light produced electron-hole pairs in the TiO₂, and the photogenerated holes that migrated to the surface repelled the Ca²⁺ ions in the solution. As a consequence, the UV irradiation suppressed the formation of a HAp thin film.     

掺锶羟磷灰石固溶体陶瓷不同孔径对成骨能力的影响

通过控制发泡剂粒径的方法制得两组孔隙率相同孔径尺寸不同的掺锶羟磷灰石多孔体陶瓷:S组平均孔径200μm;L组平均孔径750μm.植入兔桡骨缺损部位,植入后3、6和12周取材,行X线观察、大体标本观察、组织学图像观察和四环素荧光染色观察,来对比不同孔径的锶磷灰石陶瓷多孔体的骨融合能力.结果表明锶磷灰石陶瓷多孔体具有良好的生物相容性及骨传导性;两种孔径材料都有良好的成骨性能,大孔径组锶磷灰石陶瓷多孔体材料比小孔径组材料有更佳的骨修复效果;且大孔径组在12周就能观察到陶瓷材料的降解以及新生骨包绕降解陶瓷颗粒生长的现象.     

In vivo biological responses of plasma sprayed hydroxyapatite coatings with an electric polarized treatment in alkaline solution

The plasma sprayed hydroxyapatite coatings were post-treated by an electric polarized treatment in alkaline solution (PAS). The compositions, stabilities, surface charges, bone-like apatite formation abilities of the PAS coatings were investigated. The bioactivity of the PAS coatings was characterized in vivo. The results showed that the stabilities of the PAS coatings were improved because of the increased crystallinity and the decreased impurity phase. The bone-like apatite formation abilities were also improved after the PAS treatment because of the negative charges formed on the coating surfaces. Animal experiments showed that the PAS coatings could accelerate the initial fixation of the implant. The results indicated that the PAS is a promising post-treatment method to improve the biological properties of the plasma sprayed hydroxyapatite coatings.     

Influences of osmotic agents in diffusion layer on drug release from multilayer coated pellets

Nonpareil beads were coated with three different functional layers, namely inner chlorpheniramine maleate-loaded hydroxypropylmethylcellulose (HPMC, 4 mPa · s) deposition layer, middle HPMC (400 mPa · s) diffusion layer, and outer polyacrylic polymer (Eudragit RS30D) retention layer. The osmotic agents, including sodium chloride, glycine, citric acid, and disodium hydrogen phosphate, were incorporated in different amounts into the diffusion layer and the influences on drug release were studied. The osmotic agent competed with HPMC for imbibed water and subsequently caused more water influx owing to the osmotic pressure gradient. An appropriate amount of osmotic agent in the diffusion layer was necessary to exert its effect on retarding drug release. The osmotic effect on drug release was compromised with pellets at a higher coating level of the diffusion layer due to the extensive swelling and rupture of coat. The release parameters, including dissolution T_50% and mean dissolution time, showed linear relationship with osmolalities of osmotic agents studied. The effect of the osmotic agent in the diffusion layer played an important role in determining the unique multiphase drug release profiles, particularly in the initial phase of dissolution, and reduced with depletion of the osmotic agent in the later phase of dissolution.     

Facile one-pot synthesis and drug storage/release properties of hollow micro/mesoporous organosilica nanospheres

Novel hollow micro/mesoporous organosilica nanospheres (HMOSNs) of uniform diameter and shell thickness of about 90 nm and 15 nm, respectively, and with wormlike micro/mesoporous shell full of uramido groups, have been successfully fabricated by a facile one-pot route. The micro/mesoporosity of the synthesized HMOSNs has been characterized by small-angle and wide-angle X-ray diffraction (XRD), scan electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption-desorption measurements. The drug storage and release properties of the synthetic HMOSNs are measured by using ibuprofen (IBU) as a model drug, and a high drug storage capacity of 531 mg IBU per gram HMOSNs and a steady drug release behavior are exhibited.     

Incorporation of calcium salts into xanthan gum matrices: hydration,erosion and drug release characteristics

Xanthan gum (XG), a hydrophilic biopolymer with modified release properties, was used to produce directly compressed matrix tablets containing a model drug, sodium p-aminosalicylate. Three formulations were prepared, each containing a different calcium dihydrate salt: calcium chloride, calcium sulfate or dibasic calcium phosphate. The aim of the investigation was to relate the calcium ion content and solubility of the calcium salt to the in vitro drug release profile of the xanthan matrices. Tablet hydration, erosion and drug release were determined in distilled water using the British Pharmacopoeia (BP) paddle method. The data showed that the overall drug release was the greatest with addition of calcium sulfate, followed by calcium chloride and dibasic calcium phosphate. The chloride salt formulation displayed the greatest percentage erosion due to rapid mass loss during the initial phase, followed by those with sulfate or phosphate salts. As xanthan gel viscosity increased and drug release was also found to be lower, it can be concluded that drug release is influenced by the solubility of the salt present in the formulation, since these parameters determine the viscosity and structure of the gel layer.