Biomineralized polysaccharide beads for dual-stimuli-responsive drug delivery

Biomineralized polysaccharide-coated alginate beads containing PNIPAAM were prepared. The resulting beads can be used as carriers for sustained pH/temperature-sensitive drug delivery. Characterizations using SEM, EDS, FTIR, and POM revealed that the beads were covered by the calcium-phosphate-mineralized alginate/chitosan membrane. The drug-release behavior was examined using indomethacin as a model drug, and the release profile of the developed materials was found to be responsive to pH and temperature. The release profile could be sustained under neutral conditions, indicating that the mineralized polysaccharide membrane could prevent the permeability of the encapsulated drug and reduce the drug release rate.     

Efficient loading and delivery of ciprofloxacin by smart alginate/carboxylated graphene oxide/aminated chitosan composite microbeads: In vitro release and kinetic studies

New composite microbeads were formulated as smart pH-sensitive vehicle for efficient delivery of ciprofloxacin (CIP) drug. Herein, carboxylated graphene oxide (CGO) was successfully impregnated into alginate (Alg) microbeads, which were then coated with aminated chitosan (AmCs) layer to form core–shell Alg/CGO@AmCs composite microbeads. Diverse analysis tools comprising FTIR, TGA, XRD and SEM were employed to characterize the developed carriers, while their swelling profiles and pH-sensitivity were examined under different pHs. The results clarified that increasing CGO and AmCs concentrations in microbeads matrix greatly protected Alg microbeads from fast disintegration at colon pH and prolonged their swelling time. Moreover, about 94.65 % of CIP drug was successfully loaded by Alg/CGO@AmCs composite microbeads compared to 61.95 % for Alg microbeads, confirming their reduced porosity. The in vitro CIP-release profiles were investigated in simulated gastrointestinal conditions. Furthermore, increasing AmCs concentration in the outer shell of composite microbeads clearly minimized the CIP burst release at the colon region and offered a sustained release performance. Besides, the CIP release mechanism was well-described by korsmeyer-peppas kinetic model. The cytotoxicity study confirmed the potential safety of the Alg/CGO@AmCs composite microbeads with human cell viability reached 98.98 %, suggesting their applicability as smart carriers for oral delivery of antibiotics.     

Ciprofloxacin Loaded Alginate/Chitosan and Solid Lipid Nanoparticles,Preparation, and Characterization

The aim of the present study was to develop controlled drug delivery systems based on nanotechnology. Two different nanocarriers were selected, chitosan-alginate nanoparticles as hydrophilic and solid lipid nanoparticles as lipophilic carriers. Nanoparticles were prepared and characterized by evaluating particle size, zeta potential, SEM pictures, DSC thermograms, percentage of drug loading efficiency, and drug release profile. The particle size of SLNs and Chi/Alg nanoparticles was 291 ± 5 and 520 ± 16. Drug loading efficiency of Chi/Alg and SLN particles were 68.98 ± 5.5% and 88 ± 4.5%. The drug release was sustained with chitosan-alginate system for about 45 hours whereas for SLNs >98% of the drug was released in 2 hours. Release profile did not change significantly after freeze drying of particles using cryoprotector. Results suggest that under in vitro condition chitosan/alginate systems can act as promising carriers for ciprofloxacin and may be used as an alternative system in sustained delivery of ciprofloxacin.     

Study on colon-specific 5-Fu pH-enzyme Di-dependent chitosan microspheres

Colon-specific drug delivery systems (CDDS) can improve the bioavailability of drug through the oral route. A novel formulation for oral administration using pH-enzyme Di-dependent chitosan mcirospheres (MS) and 5-Fu as a model drug has been investigated for colon-specific drug delivery by the emulsification/chemical cross-linking and coating technique, respectively. The influence of polymer concentration, ratio of drug to polymer, the amount of crosslinking agent and the stirring speed on the encapsulation efficiency, particle size in microspheres were evaluated. The best formulation was optimized by an orthogonal design. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The plasma concentrations of 5-Fu after oral administration of coated chitosan MS to rats were determined and compared with that of 5-Fu solution. The in vivo pharmacokinetics study of 5-Fu loaded pH-enzyme Di-dependent chitosan MS showed sustained plasma 5-Fu concentration-time profile. The in vitro release correlated well with the pharmacokinetics profile. The results clearly demonstrated that the pH-enzyme Di-dependent chitosan MS is potential system for colon-specific drug delivery of 5-Fu.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Synthesis and characterization of a pH responsive and mucoadhesive drug delivery system for the controlled release application of anti-cancerous drug

In this work a novel pH sensitive composite, polyacrylamide grafted succinyl chitosan intercalated bentonite (AAm-g-NB/SC) was prepared as a drug carrier system for the controlled delivery of paclitaxel. Characterization of the drug delivery system was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis etc. The equilibrium swelling behaviour of the composite was studied and the result showed a maximum at pH 7.4. The in vitro drug release study of paclitaxel indicated that about 15.6% of drug release was found to be occurred at pH 1.2 within 16 h, whereas about 82.5% of drug release was occurred at the intestinal pH condition of 7.4. In vitro biocompatibility study was performed and the result showed good biocompatibility of the composite in the concentration range 6.25–100 µg/mL. The cytotoxicity assay was carried out in cancerous cell line of Human colorectal Adenocarcinoma. Mucous glycoprotein assay study showed that the drug delivery system having good apparent adhering property towards mucin. The investigation indicated that paclitaxel, an anticancer drug can be successfully entrapped in the AAm-g-NB/SC composite for the controlled and targeted delivery for colorectal cancer therapy.     

多孔β-磷酸三钙/壳聚糖/聚乙烯醇复合水凝胶的制备与性能

以NaCl为致孔剂,采用溶盐致孔法制备了多孔β-磷酸三钙/壳聚糖/聚乙烯醇（β-TCP/CS/PVA）复合水凝胶材料。 通过对比其含水率、溶胀比、拉伸强度、X射线衍射谱图、SEM和热重分析曲线,探讨了在相同环境下壳聚糖与β-磷酸三钙（β-TCP）的不同用量对聚乙烯醇(PVA)的结晶度以及对材料性能的影响。 此复合材料含水率为70%~76%。 当壳聚糖与β-TCP的质量比为2∶8时,复合材料的拉伸强度为0.56 MPa,断裂伸长率达到370%,其较好的力学性能,足以承受正常人眼压,可用作人工角膜周边支架材料。     

A novel CHS/ALG bi-layer composite membrane with sustained antimicrobial efficacy used as wound dressing

<正>A membrane composed of an alginate(ALG) layer and a chitosan(CHS) layer with sustained antimicrobial efficacy was prepared.Ciprofloxacin HC1(CIP) was incorporated into the ALG layer.Morphological feature of the composite membrane was analyzed by scanning electron microscopy(SEM).Water uptake capacity,in vitro drug release,and in vitro antimicrobial activity were evaluated.The composite membrane exhibited perfect binding characteristic between the two layers.The water uptake capacity of all the membranes was above 800%.The CIP could release from the composite membranes for 48 h.The membrane could control the bacterial growth persistently.The results suggested that this CHS/ALG composite membrane incorporated with CIP had the potential for wound dressing application.     

Synthesis and Characterization of Cyclodextrin-containing Hydrogel for Ophthalmic Drugs Delivery

Hydrogel contact lenses are ideal drug carriers for ophthalmic drugs delivery. However, some drawbacks of traditional hydrogel restricted their application in the drug delivery field. Herein, we introduced chitosan and β-cyclodextrin (β-CD) into traditional hydrogel in order to improve the properties and control drug release. β-CD functionized and crosslinkable chitosan derivative (CCH) was synthesized and introduced into HEMA/NVP monomers to form HNC tripolymer hydrogel. The introduction of CCH accelerated the polymerization of monomers. Other properties such as equilibrium swelling ratio and oxygen transmissibility of HNC hydrogel were superior to that of HN hydrogel. The capacity of HNC hydrogel to resist the protein absorption was also superior to that of HN hydrogel. Hydrogels exhibited different capacity of drug loading and releasing for different drug.     

Synthesis and characterization of folic acid‐modified carboxymethyl chitosan‐ursolic acid targeted nano‐drug carrier for the delivery of ursolic acid and 10‐hydroxycamptothecin

Carboxymethyl chitosan (CMCS), as a water‐soluble, biocompatible, and biodegradable polymer, is an excellent carrier for a sustained drug delivery system. In this study, a amphiphilic carboxymethyl chitosan‐ursolic acid nano‐drug carrier modified by folic acid (FPCU) were prepared, and then the nano‐drug carrier wrapped another anticancer drug 10‐hydroxycamptothecin were self‐assembled into nanoparticles (FPCU/HCPT NPs). The FPCU/HCPT NPs had a suitable size, high drug loading efficiency of ursolic acid (6.4%) and 10‐hydroxycamptothecin (14.1%). The drug release study in vitro indicated that the nanoparticles have obviously sustained effect and pH sensitive behaviors, the drug release amount was higher at pH 5.5 than at pH 7.4. in vitro and in vivo study showed that the nanoparticles displayed a high antitumor efficiency to tumor cells compared with free drug. The nano delivery system as a carrier for ursolic acid (UA) and 10‐hydroxycamptothecin (HCPT) has good application prospects in cancer treatment.     

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.     

Controlled release of doxorubicin from electrospun MWCNTs/PLGA hybrid nanofibers

In this study, multiwalled carbon nanotubes (MWCNTs) were used to encapsulate a model anticancer drug, doxorubicin (Dox). Then, the drug-loaded MWCNTs (Dox/MWCNTs) with an optimized drug encapsulation percentage were mixed with poly(lactide-co-glycolide) (PLGA) polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system (both PLGA polymer and MWCNTs are drug carriers) is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.     

聚(丙交酯-co-乙交酯)/β-磷酸三钙复合物的电纺研究

对生物可吸收聚(丙交酯-co-乙交酯)(poly(lactide-co-glycolide),PLGA)与β-磷酸三钙(-βTCP)复合物体系进行了电纺.研究了PLGA的浓度,-βTCP与PLGA比例,加料速度,电压,喷头与接收体之间的距离等因素对电纺过程的影响,制备出纳米纤维膜,并用扫描电镜(SEM)等对纤维膜进行表征.结果表明,电纺溶液浓度越高,或者加料速度越快,纳米纤维的直径越粗.力学实验显示,复合物中-βTCP的含量增加使纳米纤维膜的拉伸强度和杨氏模量下降.     

Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu3+) as a drug carrier

Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu) was successfully synthesized. The obtained MCS: Eu(3+) was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as the model drug. The structural, morphological, textural, and optical properties were well characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N(2) adsorption/desorption, and photoluminescence (PL) spectra, respectively. The results reveal that the MCS: Eu exhibits the typical ordered characteristics of the mesostructure. This composite shows a sustained release profile with IBU as the model drug. The IBU-loaded samples still present red luminescence of Eu(3+) ((5)D(0)-(7)F(1,2)) under UV irradiation. The emission intensities of Eu(3+) in the drug carrier system vary with the amount of released IBU, making the drug release easily tracked and monitored. The system demonstrates a great potential for drug delivery and disease therapy.     

Chitosan-Pectin Composite Gel Spheres: Effect of Some Formulation Variables on Drug Release

Chitosan-pectin composite gel spheres were prepared by ionotropic gelation method. Pectin solution containing indomethacin, a model drug, was extruded into a mixture of chitosan and calcium chloride. The release behavior of indomethacin from composite gel spheres was investigated in-vitro. The influence of factors affecting release behavior, such as type of pectin, molecular weight of chitosan, cross-linking time and release medium, were discussed in this study. Adding chitosan into gelation medium could retard the release of indomethacin from gel spheres. The different type of pectin used demonstrated slightly different drug release profiles. The higher molecular weight of chitosan showed less indomethacin release than the lower one. The increased cross-linking time slowed the drug release from composite gel spheres. The release of indomethacin from composite gel spheres was also dependent on the release medium. The drug release was slower in tris buffer where no phosphate ions which can induce the precipitation of calcium phosphate. The results suggested that the composite gel spheres of pectin and chitosan could be used as a controlled release drug delivery carrier.     

温敏性乙二醇壳聚糖水凝胶的制备及药物缓释性能

以乙二醇壳聚糖为原料, 乙酸酐为酰化剂, 通过N-乙酰化反应, 制得了新型温敏性高分子乙酰化乙二醇壳聚糖. 通过核磁共振氢谱(¹H NMR)、 傅里叶变换红外光谱(FTIR)及试管倒置法对乙酰化乙二醇壳聚糖的结构及温敏性进行了表征, 通过扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-Vis)对水凝胶的微观形貌和体外药物释放性能进行了研究. 结果表明, 随着反应时间和乙酸酐与乙二醇壳聚糖氨基摩尔比的增加, 产物的乙酰度逐渐增加; 乙酰化乙二醇壳聚糖溶液具有热可逆温敏性溶胶-凝胶转变行为, 可以通过控制乙酰化乙二醇壳聚糖的乙酰度和溶液浓度, 使溶胶-凝胶转变温度处于室温至体温(25~37 ℃)之间; 乙酰化乙二醇壳聚糖水凝胶具有“高度孔隙化且孔隙之间相互连通”的结构特点, 通过控制乙酰度和溶液浓度, 可使其孔径大小处于1~40 μm范围内; 乙酰化乙二醇壳聚糖水凝胶的乙酰度为89.90%时, 质量分数为5%~7%的水凝胶对抗癌药物吉西他滨具有缓释作用, 载药凝胶的释药时间可达3~5 d. 乙酰化乙二醇壳聚糖有望在药物释放及组织工程等领域得到广泛应用.     

Multiparticulate chitosan-dispersed system for drug delivery

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.     

Acetaminophen particle design using chitosan and a spray-drying technique

In this study matrices were prepared from particles of poorly water-soluble drugs such as acetaminophen (Act) to determine the drug release rate from these matrix particles. The matrix particles were prepared by incorporating drugs into chitosan powder (Cht, carrier) using a spray-drying method. The formation of composite particles was confirmed by scanning electron microscopic (SEM) analysis. The matrix particles prepared by spray-drying were spherical with a smooth surface. The crystallinity of acetaminophen in the composite particles was evaluated by powder X-ray diffraction and differential scanning calorimetry (DSC). The degree of crystallinity of acetaminophen in the matrix particles decreased with a reduction in the weight ratio of acetaminophen relative to the carrier. These results indicate that a solid dispersion of acetaminophen in chitosan forms matrix particles. The interaction between acetaminophen and chitosan was also investigated by FT-IR analysis. FT-IR spectroscopy of the acetaminophen solid dispersion suggested that the carbonyl group of acetaminophen and the amino group of chitosan formed a hydrogen bond. There were some differences at pH levels of 1.2 and 6.8 in the release of acetaminophen from the physical mixture compared to the matrix particles. At pH 1.2, the release from the matrix particles (Act : Cht=1 : 5) was more sustained than from the physical mixtures. The 70% release time, T70, of acetaminophen from the matrix particles (Act : Cht=1 : 5) increased in pH 1.2 fluid by about 9-fold and in pH 6.8 fluid by about 5-fold compared to crystalline acetaminophen. These results suggest that matrix particles prepared by spray-drying are useful as a sustained release preparation.     

Development of Thiolated Chitosan Nanoparticles Based Mucoadhesive Vaginal Drug Delivery Systems

The aim of the present study was to evaluate the influence of the chitosan chain length on the drug loading and releasing in VFS (vaginal fluid simulant). Thiolated chitosan nanoparticles (TCS-NPs) were prepared using thioglycolic acid and 1-ethyl-3-3-(3-dimethylaminopropyl)carbodimide hydrochloride (EDC) and characterized with FTIR. The degree of thiol substitution was found out by Ellman’s method. TCS-NPs were developed using ionic cross-linking reaction with pentasodiumtripolyphosphate (TPP). Curcumin (CUR) loaded nanoparticles were obtained by encapsulation. DLS and SEM characterized these NPs with diameter between 200 ± 50 nm. Zeta potential of NPs was 11–38 mv. The maximal encapsulation efficiency was 86.26%. The in vitro drug release studies in VFA at pH 4.2 showed a sustained release profile over a period of 3 days.     

Controlled and targeted delivery of diclofenac sodium to the intestine from pH-Responsive chitosan/poly(vinyl alcohol) interpenetrating polymeric network hydrogels

pH-Responsive hydrogels comprised of chitosan and poly(vinyl alcohol) were explored for the controlled delivery of diclofenac sodium (DS) to the intestine. To regulate the drug delivery, preformed solid inclusion complex of DS with ß-cyclodextrin (ß-CD) was added into the hydrogels. Negligible drug release was observed in the simulated gastric fluid and sustained release in the intestinal fluid. The preliminary kinetics revealed that the drug release follows anomalous transport mechanism which is influenced by the presence of ß-CD. The pH-specific release behavior of these hydrogels suggests them to be ideal candidates for oral controlled delivery of DS to the intestine.