Sweet Potato Starch Microparticles as Controlled Drug Release Carriers: Preparation and In Vitro Drug Release

The aim of this study was to investigate the in vitro drug release behavior of sweet potato starch (SPS) microparticles intended for controlled drug delivery applications. Diclofenac sodium (DS) was used as a model drug candidate in the present study. SPS microparticles were prepared using a spray-drying technique by varying the polymer concentration and drug loading. The mean particles size of drug-loaded spray-dried SPS microparticles was between 10.3 and 13.1 µm. The mean particle size increased slightly with increase in the concentration of SPS. The mean particle size of spray-dried SPS microparticles increased from 10.3 to 13.1 µm when the concentration of SPS increased from 2 to 4% w/v. Under the current spray-drying conditions, the percentage yield of spray-dried SPS microparticles did not vary much among the various formulations and it was between 65.2 and 70.1%. The encapsulation efficiencies of SPS microparticles formulations was between 95.1–98.2%, suggesting good encapsulating ability of the SPS polymer by spary drying. Drug release from all the formulations of spray-dried SPS microparticles was controlled over period of 6 h. The cumulative amount of drug release from the spray-dried SPS microparticles decreased with an increase in the concentration of SPS, while it increases as the drug loading is increased. Release of the drug from spray-dried SPS microparticles followed Fick's law of diffusion since a good correlation coefficient (R²) was observed with the Higuchi plots (R² = 0.9928 to 0.9979).     

In-vitro,ex-vivo,and in-vivo release evaluation of in situ forming buprenorphine implants using mixture of PLGA copolymers and additives

Abstract

An in-situ forming implant of buprenorphine was prepared by combining PLGA RG756s and PLGA RG504H copolymers, and additives that decreased the initial burst release. The optimum formulation was achieved based on a minimum initial burst release of BP in the in-vitro release medium using a Box-Behnken design. The in-vitro, ex-vivo, and in-vivo release of the optimized formulation was investigated. The rabbit-blood concentrations of the optimized formulation and RBP-6000 (PLGA 504H) were compared to ensure their equivalency. The results indicate that the optimized formulation can reach an effective therapeutic concentration for treating opioid dependence with minimum initial burst release.     

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization,Ex-Vivo Imaging,and In Vivo Evaluation

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CD_C-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CD_C-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CD_C-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CD_C-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.     

Spray-dried Cefixime Encapsulated Poly(lactide-co-glycolide) Microparticles: Characterization and Evaluation of In Vitro Release Kinetics with Antibacterial Activity

Our study reports on the development of novel biodegradable microparticles prepared by a spray-drying technique using the poly(lactide-co-glycolide) (PLGA), a biodegradable polymer for the controlled delivery of cefixime. Cefixime is a water-soluble drug having short biological half-life of 3 h. The behavior of PLGA in controlling drug release responses of cefixime microparticles was investigated. The resultant microparticles were characterized by scanning electron microscopy, encapsulation efficiency, particle-size distribution, X-ray diffraction, and in vitro dissolution studies (pH 7.2). To investigate the type of release mechanism that occurs, dissolution data were plotted according to different kinetic models. The in vitro release profiles from microparticles followed first order and Higuchi model release. Antibacterial studies were carried out using a standard agar diffusion method to determine the effectiveness of formulations in inhibiting the growth of microorganisms. It showed that the released drug from the formulations was effectively inhibiting the growth of microorganisms with the minimum inhibitory concentration of < 1 µg/mL. Data revealed the potential of formulations for treatment of infections caused by various microorganisms. Thus, this study demonstrates the high potential of the spray-drying technique to obtain stable cefixime microparticles with good encapsulation efficiency to achieve a delivery profile that would yield the controlled released level of the drug over a long period of time (74 h).     

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.     

5-氟尿嘧啶明胶微球的制备、表征及释药性能

为了获得粒径为50～100μm的5-氟尿嘧啶／明胶微球（5-Fu／GMs）,采用乳化一化学交联法,讨论了5-Fu用量、乳化剂浓度和水／油比等因素对微球平均粒径、载药量及包封率等的影响。结果表明,5-Fu／明胶质量比为0．5,乳化剂浓度为0．5％和水／油相体积比为1／10时,可获得最大的载药量30．1％和包封率90．2％。体外释药性能表明5-氟尿嘧啶明胶微球具有明显的药物缓释作用。     

In Situ Characterization of Catalysts Active in Partial Oxidations: TS-1 and Fe-MFI Case Studies

A concise review of the firmly established knowledge and of the unresolved problems concerning the structure and the reactivity of Ti and Fe sites in TS-1 and Fe-MFI partial oxidation catalysts is given. Some new experimental and theoretical results are also described.     

井冈霉素载药二氧化硅空心微球的原位制备及缓释性能评价

利用正硅酸乙酯在W/O乳液中的原位水解聚合,成功制备了包埋井冈霉素的二氧化硅载药空心微球. 对所得产品进行了SEM, XRD, FT-IR和粒径分布等分析,结果表明,载药空心微球粒径分布窄,范围在7.5~15 mm,球状形貌良好,具有空心结构,呈无定型态. 热重分析表明载药空心微球的药物负载量约为31.9%(w),缓释溶出实验显示载药空心微球药物释放持续时间约240 min,最终释放量达总载药量的90%以上.     

A Multioptimization Approach to Assessment of Drug Delivery of PLGA Nanoparticles: Simultaneous Control of Particle Size and Release Behavior

A multiple optimization strategy was implemented on the experimental data obtained in this study to assess drug-delivery behavior of poly(D,L-lactide-co-glycolide) (PLGA) particles. Albumin–fluorescein isothiocyanate conjugate (FITC-albumin)-loaded PLGA micro- and nanoparticles were prepared by water-in-oil-in-water double emulsion method. The experiments were carried out based on L8 Taguchi design where the effects of PLGA molecular weight, PLGA concentration in the oil phase, and sonication rate in the second emulsification step of preparation process on particle size and percentage of initial burst release of PLGA were discussed. Multioptimization toward PLGA particle size and initial burst elucidated that all aforementioned variables affect the characteristics of PLGA particles, but PLGA molecular weight was appeared as the most significant factor among studied variables. Multifarious optimizations were tested and executed varying the aforementioned factors to minimize both the size and percentage of initial burst of PLGA particles. The FTIR experiment of the optimal formulation showed the successful incorporation of the drug into the particles. These results enable careful selection and definition of optimal process parameters for the preparation of PLGA nanoparticles with sustained release properties. Furthermore, the methodology developed in this work introduces a useful tool to meet a drug delivery system with optimal release behavior.     

原位聚合法制备聚对苯二甲酸丙二醇酯／蒙脱土复合材料及其表征

采用原位聚合法制备了聚对苯二甲酸丙二醇酯(PTT)像脱土(MMT)复合材料。X射线衍射和透射电子显微镜扫描结果表明所得复合材料为剥离型或部分剥离型结构。与纯PTT、相比，由于MMT、在PTT基体中达到纳米尺寸分散，PTT／MMT复合材料的热稳定性能、结晶性能和拉伸性能都得到了明显提高。     

Synthesis of New PI/MWCNT Containing Sulfone Groups via In Situ Polymerization: Study on Thermal,Electrical, and Optical Properties

New series of polyimide (PI) nanocomposites reinforced with three different amounts of multiwalled carbon nanotubes (MWCNT; 0.5, 1, and 3 wt%) were prepared by casting, evaporation and thermal imidization. Homogeneous dispersion of MWCNT in PI matrix was investigated by transmission electron microscopy. The effects of MWCNT on the thermal properties of the PI were investigated by thermogravimetric analysis. The results showed that the thermal stability of the nanocomposites enhanced with the increasing MWCNTs content. The resultant PI/MWCNT nanocomposites were electrically conductive with significant conductivity enhancement at 3 wt% MWCNT, which is favorable for many practical uses.     

Cellulose and Xylan Based Prodrug of Diclofenac Sodium: Synthesis,Physicochemical Characterization and In Vitro Release

Present research has been made to reduce frequency of administration and increase therapeutic efficacy by developing sustained release of diclofenac sodium. In this regard, prodrugs have been synthesized by using eco-friendly “green” materials such as cellulose and xylan by activation of carboxylic acid via N,N′-carbonyldiimidazole. The polymer–drug interactions were evaluated by means of FT-IR, powder X-ray diffraction, and thermal analysis techniques. In vitro release study of synthesized prodrugs might be suggested regarding protection of drug in the upper gastrointestinal tract, and, thereby, it is expected to reach the targeted site specifically to colon.     

两亲性三嵌段共聚物的合成、表征及其药控释放行为的研究

以三硫代碳酸双(α,α′-二甲基α-″-乙酸)酯为链转移剂,以苯乙烯(St)或甲基丙烯酸甲酯(MMA)为亲油性单体,以甲基丙烯酸二甲氨基乙酯(DMA)为亲水性单体,AIBN为引发剂,通过可逆加成断裂链转移(RAFT)聚合得到两种两亲性三嵌段共聚物,通过凝胶渗透色谱(GPC)测试其组成分别为PS16-PDMA56-PS16,PMMA11-PDMA38-PMMA11,PMMA15-PDMA40-PMMA15,Mw/Mn分别为1.20、1.27、1.29。并用1HNMR进一步表征了嵌段共聚物结构。TEM及粒度测试研究发现,PS-PDMA-PS在特定溶剂中可以自组装成球形胶束,其尺寸在380 nm左右;而PMMA-PDMA-PMMA自组装成的胶束则呈均匀的球形,胶束分散较好,粒径约在120 nm左右。并研究了3种胶束对水溶性模型药物对羟基苯甲醚(HOA)的缓释效果,发现在同一时间PS-PDMA-PS胶束的累积释放量比其他胶束的小,药物的控释遵循扩散机理,并且胶束尺寸对药物的释放速率影响较大。     

Characterization of the Residual Kraft Pulp Lignin In Situ by Sulfite Treatments

Abstract

The O₂ delignification of kraft pulps from Norway spruce was shown having a significant impact on the reactivity of the residual pulp lignin as revealed from their responses to sulfite treatments at pH 7.5. A substantial higher ratio of lignin sulfonation to the phenolic hydroxyl group content of residual pulp lignin was observed for the O₂ -delignified kraft pulps (～ 0.8) as compared to a value of ～ 0.3 for the unbleached samples and ～ 1 for the spruce wood lignin. Under the prevailing sulfite treatment conditions, the sulfonation would be largely attributed to the phenolic lignin component and the etherified structures containing an α -carbonyl or -unsaturated group. The contribution from the latter units, evaluated by a borohydride pretreatment of pulps prior to the sulfite treatment, can only account for approximately 15% of the sulfonation observed for the O₂ -delignified sample. Thus, the nature of phenolic structures in the O₂ -delignified pulps was more similar to that of the wood lignin than that of the kraft pulps.     

In Situ Polymerized Poly(Amide Imide)/Multiwalled Carbon Nanotube Composite: Structural,Mechanical, and Electrical Studies

Poly(amide imide)/multiwalled carbon nanotube composites were in situ polymerized through Yamazaki–Higashi phosphorylation method, and the carboxylated multiwalled carbon nanotubes are added in the post-reaction stage. The good dispersion of multiwalled carbon nanotubes in the poly(amide imide) matrix was achieved even at 20?wt% nanotube loading. The electrical conductivity reached 33?S?m^?1; meanwhile, the tensile strength and Young’s modulus were 106MPa and 2.52?GPa, respectively. These excellent properties were contributed to the good dispersion of nanotubes and strong multiwalled carbon nanotubes–poly(amide imide) interfacial adhesions. We also demonstrate that the incorporation of multiwalled carbon nanotubes depressed the crystallization characteristics of poly(amide imide) but improve its thermal stability.     

Modification of Starch by Grafting Acetylsalicylic Acid: Synthesis,Characterization, and Application in Drug Release Domain

A series of modified starches were prepared by grafting acetylsalicylic acid (AsA) into starch by an esterification reaction then coated with poly(vinylalcohol).The structure of Starch-graft-AsA was confirmed by FTIR, NMR, and DSC. The release of AsA occurred via a retroesterification reaction of this modified coated starch (SAC) during 76 h at different pHs and AsA contents. The diffusion coefficient of AsA in the SAC matrix followed a Fickian model. The effect of AsA amount grafted on starch revealed that the higher AsA amount released was reached with SAC containing 16.18 mol% of AsA at pH 7.     

Water-Based PMMA-Nano-CaCO3 Nanocomposites by In Situ Polymerization Technique: Synthesis,Characterization and Mechanical Properties

Water-based nanocomposite was synthesized using in-situ polymerization of Methyl Methacrylate. Nano-CaCO₃ was added during polymerization along with aqueous solution of surfactant. Quantity of nano-CaCO₃ was varied as 0, 2 and 4% of monomer quantity. XRD gram shows the presence of nano-CaCO₃, which causes the crystalline nature to nanocomposites. TEM images of nano-CaCO₃ show cubic structure. Synthesis of nanocomposite follows pseudo–first-order kinetics polymerization. PMMA-4% CaCO₃ nanocomposite showed significant improvement in UV absorbance and in mechanical properties like adhesion, scratch resistance as compared to neat PMMA and 2% CaCO₃ nanocomposite.     

Design,Synthesis, Characterization,Swelling and in Vitro Drug Release Behavior of Composite Hydrogel Beads Based on Methotrexate and Chitosan Incorporating Antipyrine Moiety

Novel biodégradable pH and thermal-responsive hydrogels were prepared for controlled drug delivery studies via reaction of chitosan with 4-chloroacetylantipyrine in DMF/H₂O, followed by heating of the formed poly [acetylantipyrine-chitosan] with glutaraldehyde as a crosslinking agent to give the hydrogels. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25°C, 37°C and 45°C) in solutions of pH 2.1 and 7.4. Methotrexate (MTX) was entrapped in the hydrogels, and drug release studies were carried out at 37 °C in solutions at pH 2.1 and 7.4.