Controlled drug delivery systems based on thiolated chitosan microspheres

The aim of the present study was to verify the potential of chitosan-thio-butyl-amidine (TBA) microspheres as carrier systems for controlled drug delivery. In this study microspheres were prepared utilizing water in oil (w/o) emulsification solvent evaporation technique. A concentration of 0.5% of chitosan-TBA conjugate displaying 100 µM thiol groups per gram polymer was used in the aqueous phase of the emulsion in order to prepare microspheres. The obtained non-aggregated free-flowing microspheres were examined with conventional light microscope as well as scanning electron microscopy (SEM). The microscopic images indicated that the prepared chitosan-TBA microspheres were of spherical shape and smooth surface while microparticles obtained from the unmodified chitosan were of porous structure and non-spherical shape. Particle size distribution was determined to be in the range from 1 to 59 µm. The free thiol group content of chitosan-TBA microspheres prepared with an aqueous phase of pH 2, 5, and 6.5 were determined to be 71.4, 49.4, and 8.2 µM/g polymer, respectively. Furthermore, results attained from in vitro release studies with fluorescein isothiocyanate labelled dextran (FITC-dextran) loaded chitosan-TBA microspheres showed a controlled release rate for more than three hours while the control reached the maximum peak level of release already within an hour. According to these results, chitosan-TBA microspheres seem to be a promising tool in transmucosal drug delivery for poorly absorbed therapeutic agents.     

超声辅助复乳法制备多孔羟基磷灰石微球的研究

采用超声辅助复乳法制备多孔HAP微球,通过调节反应温度、时间和pH值条件,获得了粒径分布均匀、形貌规则,具有不规则纳米多孔结构的HAP微球。通过XRD、IR、SEM、TEM对微球进行了表征,研究了实验条件对产物成分及形貌的影响。结果表明,适宜的合成条件为:反应温度50℃,反应时间24h,内水相pH值≥10,在此条件下制备的产物为球形HAP粒子,直径分布在50~200nm之间,尺寸比较均一,每个微球由大量的纳米HAP粒子堆积而成,微球呈现疏松多孔结构。这种多孔HAP微球在骨组织修复及药物控释材料方面具有应用前景。     

Evaluation of PLGA microspheres as delivery system for antitumor agent-camptothecin

Camptothecin (CPT) and its analogues are a new class of anticancer agents that have been identified over the past several years. Camptothecin exists in two forms depending on the pH: An active lactone form at pH below 5 and an inactive carboxylate form at basic or physiological neutral pH. Poly(lactide-co-glycolide) (PLGA) microspheres have been considered good delivery vehicles for CPT because of acidic microenvironment formed through PLGA degradation. The objective of this study is to investigate antitumor activity of CPT after it is encapsulated in PLGA microspheres. In this study, PLGA microspheres containing various CPT loadings were prepared and characterized. Cytotoxicity of these microspheres to B16 melanoma cells was then evaluated, and uptake of microspheres by B16 cells was also studied. Analysis of drug stability revealed that CPT is released from the microspheres in its active lactone form over the entire release duration. It was also found that there was no interaction between CPT and PLGA matrix within microspheres through Differential Scanning Calorimetry (DSC) and Fourien Transform Infrared Spectroscopy (FT-IR) and hign performance liquid chromatography (HPLC) studies. Cytotoxicity assay showed that CPT encapsulated in PLGA microspheres still retained its antitumor potency. Uptake study revealed quick uptake of the microspheres by B16 cells, which was desirable. It was concluded that PLGA microspheres were suitable delivery vehicles to stabilize and deliver CPT for the treatment of cancer.     

One-pot synthesis of HA-coated gelatin microspheres by an emulsion method

A one-pot strategy was firstly presented in this paper to prepare gelatin-hydroxyapatite (HA) composite microspheres with a core-shell structure in an inverse emulsion. The FT-IR and XRD analysis confirmed the unique formation of HA on the surface of the gelatin microspheres. The deposited HA particles of about 50 nm in size were found to be approximately spherical in morphology and poorly crystallized. When the weight ratio of HA to gelatin was less than 1:4, most of the HA particles were precipitated on the surface of the gelatin spheres to form a homogeneous coating of about 100 nm in thickness. Moreover, the resulting core-shell composite microspheres had a good dispersity and displayed a particle size distribution of 5-40 μm.     

无皂乳液聚合法制备单分散聚苯乙烯微球

以苯乙烯（St）为单体,过硫酸钾（KPS）为引发剂,采用无皂乳液聚合法制备了聚苯乙烯微球。研究了单体、引发剂的浓度,引发剂加入方式,聚合温度对制备PS微球粒径的影响。运用傅立叶红外光谱（FT-IR）、透射电子显微镜（TEM）、场发射扫描电镜（FE-SEM）、电势与纳米粒径分析仪等手段,对微球的组成成分、表面形态、粒径及其分布、表面电势进行了表征。结果表明微球粒径均匀,在100-200nm范围内,球形度良好且呈单分散性。     

无皂乳液聚合法制备PS/TiO2核-壳复合微球

采用无皂乳液聚合法制备聚苯乙烯(PS)微球,将所制备的PS微球经磺化吸水后,利用钛酸丁酯作前驱体在乙醇中反应,使TiO2包覆在磺化苯乙烯微球表面,得到有机-无机PS/TiO2复合微球。在所得的杂化微球表面接枝上可聚官能团,利用无皂乳液聚合将聚甲基丙烯酸甲酯聚合到微球表面,得到核-壳-壳杂化微球。用FT-IR、SEM和TGA等方法对所制得的复合微球进行表征。结果表明PS、PS/TiO2及PS/TiO2/PMMA微球表面光滑,球形度好,单分散性良好;通过改变TBOT的加入量可以控制TiO2对PS微球的包覆厚度。     

Development and in vitro characterization of chitosan-based microspheres for nasal delivery of promethazine

Conventional and composed promethazine-loaded microspheres were prepared by spray drying of chitosan solution systems and double water-in-oil-in-water (W/O/W) emulsion systems, respectively. Double emulsions were prepared in two different feed concentrations, with chitosan dissolved in both water phases, and ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the microspheres depended on the chitosan content, type and the feed concentration of spray-dried system. Results obtained suggested that better ethylcellulose microcapsules with promethazine in the chitosan matrix were formed when less concentrated emulsion systems were spray-dried. Thus, in case of such a system, with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release was obtained.     

石油沥青对乳化法煤沥青基炭微球的改性机理

通过在煤焦油沥青中添加石油沥青获得沥青甲苯胶体溶液,然后与聚乙烯醇(PVA)的甘油溶液乳化,制备了煤沥青基炭微球.为了阐明沥青在甲苯中的溶解性及其与PVA中憎水的亚甲基亲合力对于微球形成的影响,在煤沥青中添加了不同比例的与PVA中憎水的亚甲基更具亲合力的石油沥青,建立了一个微球成形机理的模型.研究发现,添加石油沥青可以促进乳化液中沥青分子与分散剂界面上表面活性剂分子的取向稳定性,从而明显改善沥青微球的球形度.石油沥青的添加降低了混合后沥青的软化点,为使沥青微球的软化点高于空气氧化始温,需要选择适当的添加比例.     

Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method

We have prepared polymeric drug nanoparticles by oil in water (O/W) emulsion solvent evaporation method. We used acetone as solvent for polymer and water as non-solvent. The purpose of this study is to use the emulsion solvent evaporation method in order to prepare nanoparticles and to investigate the effects of the various processing parameters to the characteristics of the nanoparticles. In this research, we use two different forms of acrylic polymers, Eudragit E100 and Eudragit RS. It was found that the size of the nanoparticles depends on different parameters such as the polymer concentration in the organic solvent, surfactant concentration and the volume ratio of oil and water phases. The morphology structure is investigated by transmission electron microscope (TEM). TEM images confirmed that the nanoparticles produced were spherical in shape and the successfully prepared nanoparticles with size 80?nm. The size distribution is measured by laser dynamic light scattering. The size distribution of the nanoparticles was found in the range from 50 to 150?nm. Investigation of Fourier transform infrared spectroscopy indicated the absence of the interactions between the drug and polymer. X-ray diffraction patterns of nanoparticles containing ketoprofen, Eudragit E100 and Eudragit RS showed the amorphous structure.     

Calcium phosphate/block copolymer hybrid porous nanospheres: Preparation and application in drug delivery

Calcium phosphate (CaP)/block copolymer hybrid porous nanospheres were synthesized by a simple solution method using CaCl₂ and (NH₄)₂HPO₄ in the presence of a block copolymer at room temperature. X-ray diffraction showed that the sample consisted of amorphous calcium phosphate (ACP). The BET specific surface area and the pore size distribution of the CaP/PLLA-mPEG hybrid porous nanospheres were also characterized. The as-prepared CaP/PLLA-mPEG hybrid porous nanospheres were explored as drug carriers, and showed a high ibuprofen loading capacity and in vitro prolonged drug release behavior in a simulated body fluid. These CaP/block copolymer hybrid porous nanospheres exhibit a great potential for application in drug delivery.     

Microneedles for transdermal drug delivery: a systematic review

Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500?Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.     

氧化海藻酸钠交联壳聚糖载药复合体系的制备及其药物缓释初步研究

为获得一种新型的药物释放复合体系,本实验首先通过乳化交联法制备壳聚糖(CS)包载四环素(TC)微球,然后利用氧化海藻酸钠交联聚磷酸钙/壳聚糖(CPP/CS)复合材料,用冷冻干燥法制备了载药微球复合体系.并用傅立叶红外光谱仪(IR)、扫描电镜(SEM)及药物的体外释放等方法对该载药微球复合体系进行分析和表征.结果显示,经...     

Pickering乳液聚合制备中空聚苯乙烯复合微球

通过改进Stber法制得纳米SiO2,并经硅烷偶联剂改性使其表面具有较佳两亲性,以该两亲性纳米粉体为油/水界面稳定剂构建O/W型Pickering乳液,引发油相中的苯乙烯单体聚合,在不同苯乙烯与成孔溶剂正辛烷的比例下制得了SiO2/聚苯乙烯复合微球;经傅里叶红外变换光谱(FTIR)、凝胶渗透色谱-多角度激光光散射仪(GPC-MALLS)、热失重分析仪(TGA)、扫描电子显微镜(SEM)及透射电子显微镜(TEM)检测,证实复合微球具有中空的结构特点,并依此讨论了中空微球的形成机理。     

Preparation and evaluation of mucin-gelatin mucoadhesive microspheres for rectal delivery of ceftriaxone sodium

Soluble mucin (S-mucin) processed from the small intestines (ileal region) of freshly slaughtered pigs via homogenization, dialysis, centrifugation and lyophilization and its admixtures with type A gelatin were dispersed in an aqueous medium and used to formulate ceftriaxone sodium-loaded mucoadhesive microspheres by the emulsification cross-linking method using arachis oil as the continuous phase. The release profile of ceftriaxone sodium from the microspheres was evaluated in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). The microspheres were further evaluated as possible novel delivery system for rectal delivery of ceftriaxone sodium in rats. Release of ceftriaxone sodium from the microspheres in both release media was found to occur predominantly by diffusion following non-Fickian transport mechanism and was higher and more rapid in SIF than in SGF. The results obtained from this study may indicate that ceftriaxone sodium could be successfully delivered rectally when embedded in microspheres formulated with either type A gelatin alone or its admixtures with porcine mucin; hence providing a therapeutically viable alternative route for the delivery of this acid-labile third generation cephalosporin.     

Ultra-small MoS_2 nanodots-incorporated mesoporous silica nanospheres for pH-sensitive drug delivery and CT imaging

Functionalization of mesoporous silica spheres with well-dispersed and ultra-small nanodots to exert their synergistic effects for biomedical applications has been considered to be an urgent challenge.Herein,homogeneously incorporation of ultra-small and monodispersed MoS₂ nanodots in the mesoporous silica nanospheres(MSN)was achieved by a facile one-step solvothermal reaction.The as-synthesized UsMSND@MSN possessed uniform size(~115 nm)and favorable biocompatibility inherited from MSN.The dispersed UsMSND within MSN could act as anchoring sites for aromatic anti-cancer drug DOX loading,and consequently achieved pH-responsive release based on the specialπ-π/electrostatic interactions with the DOX molecules.More importantly,the well-dispersed UsMSND in MSN could function as the non-toxic contrast agent for the sensitive in vivo CT imaging in various tumors including breast cancer and glioma with different sections.This work promises a good strategy for dispersed incorporation of UsMSND into MSN as an excellent pH-responsive platform for simultaneous cancer imaging and therapy.     

Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes

Background: The aim of this study was to develop chitosan microspheres for nasal delivery of ondansetron hydrochloride (OND). Method: Microspheres were prepared with spray-drying method using glutaraldehyde as the crosslinking agent. Microspheres were characterized in terms of morphology, particle size, zeta potential, production yield, drug content, encapsulation efficiency, and in vitro drug release. Results: All microspheres were spherical in shape with smooth surface and positively charged. Microspheres had also high encapsulation efficiency and the suitable particle size for nasal administration. In vitro studies indicated that all crosslinked microspheres had a significant burst effect, and sustained drug release pattern was observed until 24 hours following burst drug release. Nasal absorption of OND from crosslinked chitosan microspheres was evaluated in rats, and pharmacokinetic parameters of OND calculated from nasal microsphere administration were compared with those of both nasal and parenteral administration of aqueous solutions of OND. In vivo data also supported that OND-loaded microspheres were also able to attain a sustained plasma profile and significantly larger area under the curve values with respect to nasal aqueous solution of OND. Conclusion: Based on in vitro and in vivo data, it could be concluded that crosslinked chitosan microspheres are considered as a nasal delivery system of OND.     

A simple method of microneedle array fabrication for transdermal drug delivery

Abstract

The outermost layer of skin, stratum corneum, being lipophilic limits the passive transport of hydrophilic and large molecular weight drugs. Microfabrication technology has been adapted to fabricate micron scale needles, which are minimally invasive, yet able to deliver the drugs across this barrier layer. In this study, we fabricated microneedles from a biocompatible polymer, namely, poly (ethylene glycol) diacrylate. A simple lithographical approach was developed for microneedle array fabrication. Several factors including polymerization time, ultraviolet light intensity and distance from light source were studied for their effects on microneedle formation. The microneedle length and tip diameter can be controlled by varying these factors. The microneedles were shown to be able to penetrate cadaver pig skin. Model drug rhodamine B was encapsulated in the range of 50 µg to 450 µg per microneedle array. The fabricated microneedles containing rhodamine B increased the permeability by four times than the control. Altogether, we demonstrated that the microneedle arrays can be fabricated through a simple single-step process and needles were mechanically strong to penetrate skin, increasing the permeability of encapsulated drug through skin.     

Application of materials as medical devices with localized drug delivery capabilities for enhanced wound repair

The plentiful assortment of natural and synthetic materials can be leveraged to accommodate diverse wound types, as well as different stages of the healing process. An ideal material is envisioned to promote tissue repair with minimal inconvenience for patients. Traditional materials employed in the clinical setting often invoke secondary complications, such as infection, pain, foreign body reaction, and chronic inflammation. This review surveys the repertoire of surgical sutures, wound dressings, surgical glues, orthopedic fixation devices and bone fillers with drug eluting capabilities. It highlights the various techniques developed to effectively incorporate drugs into the selected material or blend of materials for both soft and hard tissue repair. The mechanical and chemical attributes of the resultant materials are also discussed, along with their biological outcomes in vitro and/or in vivo. Perspectives and challenges regarding future research endeavors are also delineated for next-generation wound repair materials.     

用于肺部给药的壳聚糖空心微球的制备

采用壳聚糖为壁材、烷基多糖苷为赋形剂通过喷雾干燥的方法成功制备出了可用于肺部给药的空心载药微球,其粒径在10μm左右。采用扫描电子纤维镜观察了所得粒子的形貌,并分析了喷雾干燥条件下得到这种薄壁空心结构的原理。     

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity.Here we report a dendronized polymer-doxorubicin(DOX)hybrid(DPDH)with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate(LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4.DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis.Owing to the dendronzied structure,DPDH has a significantly longer blood circulation time than LPDC.DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological analysis.Biosafety of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological analysis.This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.