A spheres-in-sphere structure for improving protein-loading poly (lactide-co-glycolide) microspheres

In present study, protein loaded poly (lactide-co-glycolide)/chitosan microspheres (PLGA/CS MSs) with spheres-in-sphere structure were prepared in order to weaken the burst release of protein from PLGA microspheres (PLGA MSs) and to buffer acidic micro-milieu. The PLGA MSs and PLGA/CS MSs were characterized in terms of their size distribution, morphology, drug-loading rate, zeta potential and physical-chemical properties. The incubation experiments of PLGA MSs and PLGA/CS MSs were manipulated in PBS solution at pH 7.4, 37 °C to monitor the release of BSA and the vehicles degradation. The release kinetic of BSA was illuminated mainly based on the degradation processes of the matrices. External CS crusts were proved to strikingly improve the release kinetic of the model protein by reducing initial burst release and extending continuous release while acting as a diffusion barrier. Moreover, using PLGA/CS MSs could avoid the decrease of pH value resulted from the acidic products of PLGA MSs because of the effective buffer action of the basic groups in CS. The results demonstrated that the spheres-in-sphere structure is an effective way to control the initial burst release of protein and to overcome the acidic problem of protein-loading PLGA MSs.     

Thermal characterization of poly(lactide-co-glycolide) microspheres containing bupivacaine base polymorphs

Solid-state chemistry of bupivacaine base, obtained by precipitation from bupivacaine hydrochloride solutions with ammonia, was investigated. Two bupivacaine base polymorphs (Form I: T _m=105.6±0.0°C; Form II: T _m=97.6±0.2°C) were isolated depending on the precipitation conditions and characterised by thermal analysis and FTIR spectroscopy. No weight loss was evidenced by TG confirming that no solvate formation had occurred. Biodegradable poly(lactide-co-glycolides) microspheres containing bupivacaine base were prepared by spray-drying. In the microspheres bupivacaine base was present as the metastable low melting crystal form independently of the bupivacaine base / poly(lactide-co-glycolides) ratio.     

Mechanism of preparing monodispersed poly(acrylamide/methacrylic acid) microspheres in ethanol. II

We previously established a new mechanism of monodispersed poly(acrylamide/methacrylic acid) (PAAm/MAA) microspheres on the basis that the minimonomer droplets of AAm/MAA complexes were formed in ethanol at a polymerization temperature of 60 °C prior to the polymerization. Here, the effects of various factors such as the types and amount of initiators and crosslinking agents on the average diameters and morphologies of PAAm/MAA microspheres were qualitatively discussed on the basis of the new mechanism. The partition of reagents between the minimonomer droplets and the continuous medium was particularly emphasized in discussion because the formation of microspheres occurred in the minimonomer droplets. The new mechanism suggested that the size (number) and morphologies of the microspheres as well as the polymerization kinetics were consequently dependent on the properties and amount of initiators, crosslinking agents, and other monomers. It successfully explained the experimental phenomenon observed thus far in precipitation or dispersion polymerizations that the average diameter of microspheres is increased with the increase of the concentration of initiators, which contradicted the prediction of conventional mechanisms. As an example, the initiator dimethyl 2,2′‐azobisisobutyrate (DMAIB) was dominantly partitioned in ethanol. Thus, the diameter of the PAAm/MAA microspheres was decreased with the increase of the concentration of DMAIB because the formation of microspheres depended on the adsorption of free radicals to the minimonomer droplets. However, the initiator 4,4′‐azobis‐4‐cyanovaleric acid was dominantly partitioned within the minimonomer droplets, thereby increasing the diameter of the microspheres as the concentration of initiator was increased because of the lower efficiency of free radicals. Relative to the initiators, the crosslinking agents showed inverse effects on the diameter and morphology of the microspheres according to the different partitions. The monomer was transferred by the incorporation of minimonomer droplets with growing microspheres. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2833–2844, 2004     

Synthesis of monodispersed poly(acrylonitrile) microspheres by dispersion polymerization in compressed liquid dimethyl ether

In this study, monodispersed spherical particles of poly(acrylonitrile) were synthesized via dispersion polymerization in compressed liquid dimethyl ether using 2,2′-azobisisobutyronitrile (AIBN) as an initiator and five kinds of surfactants: PDMS-g-pyrrolidonecarboxylic acid (Monasil PCA™), PDMS modified surfactants, SS-5050K™, KF-6017™, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafluorodecyl acrylate), and poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl methacrylate). Using Monasil PCA as a surfactant, uniform and spherical polymer particles were generated. The size of the microsphere particles was reduced via an increase in the concentration of Monasil PCA and a reduction in the monomer concentration. Increases in the concentration of AIBN resulted in a broad distribution of microspheres. Reaction temperature and pressure did not exert significant effects on the size and size distribution of the polymer particles.     

Preparation of submicrometer-sized monodispersed thermoresponsive core-shell hydrogel microspheres

We have successfully prepared monodispersed thermoresponsive core-shell hydrogel microspheres with a mean diameter of 200-400 nm with poly(N-isopropylacrylamide-co-styrene) [P(NIPAM-co-St)] cores and poly(N-isopropylacrylamide) (PNIPAM) shells. The submicrometer-sized monodispersed P(NIPAM-co-St) core seeds were prepared by using a surfactant-free emulsion polymerization method, and the PNIPAM shell layers were fabricated onto the core seeds by using a seed polymerization method. The particle size, morphology and monodispersity, and thermoresponsive characteristics of the prepared microspheres were experimentally studied. In the preparation of P(NIPAM-co-St) seeds, with increasing the initiator dosage, the mean diameters and the dispersal coefficients were almost at the same levels at first; however, when the initiator dosage increased further to a critical amount, the mean diameters decreased drastically and the monodispersity became worse significantly. With increasing the stirring rate, the particle diameter decreased, and when the stirring rate was larger than 600 rpm, the monodispersity became worse obviously. With increasing the phase ratio, the mean diameter became larger simply, and the monodispersity became worse first and then became better again. With increasing the reaction time, the particle sizes nearly did not change, while the monodispersity gradually became better slightly. For the core-shell microspheres, with increasing the NIPAM dosage in the preparation of the PNIPAM shell layers, the mean diameters became larger simply, the monodispersity became better, and the thermoresponsive swelling ratio of the hydrodynamic diameters increased.     

Preparation and surface modification of magnetic poly(methyl methacrylate) microspheres

~~Preparation and surface modification of magnetic poly(methyl methacrylate) microspheres~~     

Preparation and properties of poly(phosphonatoalanes)

Two general types of poly(phosphonatoalanes), [? Al(X)O? P(O)(R)O? ]_n (X = Cl or F, R = alkyl or aryl) and [? Al(OP(O)R₂)O? P(O)(R′)O? ]_n, were prepared and studied. Poly[chloro(phosphonato)alanes] are influsible and have low molecular weights (n = 4–11). Polyfluoro(phosphonato)alanes are fusible and also have low molecular weights, but under certain conditions grow to higher polymers (n = 30–45). Poly[phosphinato(phosphonato)alanes] are fusible and are prepared with high molecular weights (n = 83–340).     

PVA-g-PS复合微球的制备与粒径控制研究

由链转移自由基聚合与端基置换反应法,合成了苯乙稀基单封端的聚醋酸乙烯酯(PVAc)大分子单体,使其与苯乙烯在乙醇/水的混合介质中进行自由基分散共聚,得到了表面以PVAc为接枝链的聚苯乙烯(PVAc-g-PSt)微球。将所得微球在碱性条件下醇解,形成了以亲水性聚乙烯醇(PVA)为壳、聚苯乙烯为核的复合微球(PVAc-g-PSt)。用核磁共振对聚合物的结构进行表征,定出了PVAc末端双键的含量;并用激光光散射、扫描电子显微镜对微球的粒径与形态进行了表征。研究结果表明,在共聚反应体系中大分子单体的分子量与浓度、苯乙烯浓度、引发剂浓度及溶剂的组成对微球的形态和粒径大小有明显影响。     

Biocompatibility properties of composite scaffolds based on 1,4-butanediamine modified poly(lactide-co-glycolide) and nanobioceramics

Three-dimensional biodegradable porous scaffolds play an important role in tissue engineering. The degradable scaffold material, based on 1,4-butanediamine-modified poly(lactide-co-glycolide) (BMPLGA), nano-bioactive glass (NBAG), and nano-β-tricalciumphosphate (β-TCP), was prepared by a solution-casting/salt-leaching method. The biological properties were studied by using cell cytotoxicity, von Kossa staining, alkaline phosphatase activity, hemolytic test, acute toxicity, and genetic toxicity test. The MTT results indicated that the BMPLGA/NBAG-β-TCP materials did not show any cytotoxicity. The result of von Kossa staining showed that the introduction of the NBAG and β-TCP promoted fibroblastic differentiation and improved the mineral deposition of the BMPLGA matrix. In addition, the presence of NBAG and β-TCP in the composite further enhanced the ALP activity in comparison with the sole BMPLGA material. The hemolytic potential showed that the nanocomposite scaffolds were non-hemolytic. The BMPLGA/NBAG-β-TCP scaffolds showed no acute systemic toxicity or mutagenic action. Therefore, the results indicated the BMPLGA/NBAG-β-TCP nanocomposite scaffold could be considered as a potential bone tissue engineering implant.     

Preparation and properties of poly(imide-oxoisoindolobenzothiadiazine dioxides)

New thermally stable poly(imide-oxoisoindolobenzothiadiazine dioxides) (PIOD) have been prepared by the three-step cyclopolycondensation reaction of diaminobenzenesulfonamides with aromatic tetracarboxylic dianhydrides. The polymerization proceeded through the formation of poly(amic acid-sulfonamides) (PAAS), followed by cyclodehydration to yield polyimide-sulfonamides (PIS), which were subsequently converted to PIOD at 300°C. PAAS having inherent viscosities in the range of 0.1–0.5 in N-methyl-2-pyrrolidone (NMP) were obtained in approximately quantitative yield. PIOD were insoluble in most organic solvents, whereas PAAS and PIS were soluble in NMP and dimethyl sulfoxide. Differential thermal analysis and thermogravimetric analysis indicated that PIOD began to decompose at 460°C in air. The cyclodehydration of the model compounds was also investigated.     

Preparation and properties of poly(methylene terephthalates)

A systematic study of poly(methylene terephthalates) has been made. Melting points, second-order transition temperatures, and solubility temperatures are presented for the homologous series of terephthalate polyesters of ethylene glycol through 1,10-dodecanediol, and for terephthalate copolyesters of: (1) ethylene glycol/1,3-propanediol and (2) ethylene glycol/1,4-butanediol. Fiber properties of the terephthalate polyesters and the 70/30 ethylene glycol/1,3-propanediol copolyterephthalate ester are presented. Only the first three members of the poly(methylene terephthalate) series show promise for use in textile fibers.     

Preparation, characterization, and pharmacodynamics of exenatide-loaded poly(DL-lactic-co-glycolic acid) microspheres

Exenatide (synthetic exendin-4), a 39-amino acid peptide, was encapsulated in poly(DL-lactic-co-glycolic acid) (PLGA) microspheres as a sustained release delivery system for the therapy of type 2 diabetes mellitus. The microspheres were prepared by a double-emulsion solvent evaporation method and the particle size, surface morphology, drug encapsulation efficiency, in vitro release profiles and in vivo hypoglycemic activity were evaluated. The results indicated that the morphology of the exenatide PLGA microspheres presented as a spherical shape with smooth surface, and the particle sizes distributed from 5.8 to 13.6 μm. The drug encapsulation efficiency tested by micro-bicinchoninic acid (BCA) assay was influenced by certain parameters such as inner and outer aqueous phase volume, PLGA concentration in oil phase, polyvinyl alcohol (PVA) concentrations in outer aqueous phase. Moreover, in vitro release behaviors were also affected by some parameters such as polymer type, PLGA molecular, internal aqueous phase volume, PLGA concentration. The pharmacodynamics in streptozotocin (STZ)-induced diabetic mice suggested that, exenatide microspheres have a significant hypoglycemic activity within one month, and its controlling of plasma glucose was similar to that of exenatide solution injected twice daily with identical exenatide amount. In conclusion, this microsphere could be a well sustained delivery system for exenatide to treat type 2 diabetes mellitus.     

Preparation and properties of alkylated poly(styrene-graft-ethylene oxide)

Poly(styrene-graft-ethylene oxide), having alkyl chains (C₁₂ or C₁₈) on the polystyrene main chain or on the poly(ethylene oxide) (PEO) side chains, were synthesized. The main chain was alkylated by first ionizing amide groups in a styrene/acrylamide copolymer with tert-butoxide, and then using the amide anions as sites for reactions with 1-bromoalkanes. An excess of amide anions was used in the reaction, and the remaining anions were subsequently utilized as initiator sites for the anionic polymerization of ethylene oxide (EO). Synthesis of poly(styrene-graft-ethylene oxide) with alkylated side chains was accomplished by polymerization of EO onto the ionized styrene/acrylamide copolymer, followed by an alkylation of the terminal alkoxide anions with 1-bromoalkanes. The alkylated graft copolymers were structurally characterized by using elemental analysis, ¹H NMR, GPC, and IR spectroscopy. DSC analysis showed that only graft copolymers with PEO contents exceeding about 50 wt % and side chain crystallinities comparable to those of homo-PEO. Main chain alkylated graft copolymers generally had higher crystalinities, as compared to nonalkylated and side chain alkylated samples. The graft copolymers absorbed water corresponding to one water molecule per EO unit at low PEO contents. The water absorption increased progressively at PEO contents above 30 wt % for main chain alkylated samples and above 50 wt % for non-alkylated samples. © 1995 John Wiley & Sons, Inc.     

Preparation of monodispersed polystyrene microspheres uniformly coated by magnetite via heterogeneous polymerization

Composite microspheres of core-shell type were prepared by a seeded polymerization using monodispersed polystyrene seed latex (Ps) combined with an in situ dispersion of magnetite (Fe₃O₄) fine particles. The heterogeneous polymerization was carried out in aqueous dispersions of the Fe₃O₄ particles modified with sodium oleate. All the synthetic processes were carried out in a wet state to avoid serious agglomeration. The morphology of the composite particle and the size distribution were examined to discuss the effects on the polymerization parameters, such as monomer concentration, type and concentration of an initiator, magnetite particle concentration and the method of surface modification of Fe₃O₄.     

Superabsorbent poly(acrylamide-co-itaconic acid) hydrogel microspheres: Preparation,characterization and absorbency

Poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) hydrogel microspheres were prepared via inverse suspension polymerization method. DLS results showed the formation of the monodispersed hydrogel microspheres. The size of the hydrogel microspheres could be controlled by polymerization parameters. Absorbencies of P(AM-co-IA) microspheres in water and saline were investigated and calculated by size changes of each particle before and after swelling. The results showed that P(AM-co-IA) had high absorbencies, the weight of swollen particles was above 4000 times to that of the original dried microspheres. The superabsorbent hydrogel microspheres might find the potential applications in the fields of soil amendments, water shutoff agents, and drug delivery carriers.     

Preparation of narrow or monodisperse poly(ethyleneglycol dimethacrylate) microspheres by distillation-precipitation polymerization

Highly crosslinked narrow or monodisperse poly(ethyleneglycol dimethacryltae) (polyEGDMA) microspheres were prepared by distillation-precipitation polymerization in neat acetonitrile with 2,2′-azobis(2-methyl propinitrile) (AIBN) as an initiator. The polymer microspheres with clean surfaces due to the absence of any added stabilizer in the reaction system were formed simultaneously through a precipitation manner during the distillation of acetonitrile off the reaction system. The effects of the solvent, initiator concentration, monomer concentration and comonomer (divinylbenzene, DVB) fraction on the formation of the microspheres were investigated. Narrow- or monodisperse particles with spherical shape and smooth surface were obtained with diameters between 1.18 and 2.50 μm with monomer loading lower than 3.13 vol%. The surfaces of the microspheres became rougher, some elliptic particles and doublet or triplet appeared with the increase of monomer concentration (as high as 3.75 vol%). The yield of polymer microspheres was increased from 31% to 75% with the increase of EGDMA fraction from 0 to 100% when EGDMA was copolymerized with DVB. The resulting polymer microspheres were characterized with scanning electron microscope (SEM) and Fourier transform-IR spectra.     

Preparation and properties of photocrosslinkable poly(2-vinyloxyethyl cinnamate)

Photocrosslinkable poly(2-vinyloxyethyl cinnamate)'s with substituents in para position of cinnamoyl moieties were prepared cationically. Polymerizability of the monomers was markedly governed by the substituent and the glass transition temperatures of the polymers varied in the range of about 0 to 72°C. The photocrosslinking mechanism in relation to the photosensitivity of the polymers is discussed on the basis of spectroscopical studies.