Preparation of biodegradable microspheres by anionic dispersion polymerization with PLA copolymeric dispersion stabilizer

We prepared poly(d,l-lactide) (PLA) microspheres by anionic dispersion polymerization of d,l-lactide. The polymerization was carried out in xylene/heptane (1:2 in v/v) mixture solution at 368 K for 9 h, with poly(dodecyl methacrylate)-co-poly[α-methacryloxyethoxy-poly(l-lactide)] (PDMA-co-P(MA-PLLA)) synthesized in this study, as a dispersion stabilizer. The number-averaged diameter and diameter distribution (coefficient of variation) of obtained PLA microspheres ranged from 180 to 800 nm and 14–40%, respectively, depending on the preparation condition. Furthermore, the time courses of monomer conversion, particle diameter, and particle number were investigated to clarify the formation mechanism of microspheres with PDMA-co-P(MA-PLLA) as a dispersion stabilizer. From this experiment, we found that the aggregation of primary particles occurred in anionic dispersion polymerization, and the particle diameter of obtained PLA microspheres decreased with increasing PDMA-co-P(MA-PLLA) concentration. In conclusion, we clarified that PDMA-co-P(MA-PLLA) effectively contributed to the stability of primary particles.     

Role of dispersion stabilizer with hydroxy groups in preparation of monodisperse polylactide microspheres

Monodisperse poly(D ,L ‐lactide) (PDLLA) microspheres were prepared by dispersion polymerization of D ,L ‐lactide in xylene/heptane (1/2, v/v) with poly[(dodecyl methacrylate)‐co‐(2‐hydroxyethyl methacrylate)] (P(DMA‐co‐HEMA)) as a dispersion stabilizer. P(DMA‐co‐HEMA) contains hydroxy groups, which act as an initiation group for pseudoanionic dispersion polymerization. The best coefficient of variation (CV) values concerning particle diameter distribution and the particle diameter of obtained PDLLA microspheres were 3.7% and 5.3 μm, respectively. The particle diameter decreased with increasing concentration of P(DMA‐co‐HEMA) and HEMA maintained low CV (<10%) values. As a result, monodisperse PDLLA microspheres ranging from 1.3 to 5.3 μm were obtained. In addition, it was found that monodisperse PDLLA microspheres were obtained by sufficient capture of growing polymers and monomers in the particle growth stage. Therefore, the HEMA concentration in P(DMA‐co‐HEMA) strongly affecting the capturing capability is the most important factor. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5230–5240, 2009     

Preparation of Monodisperse Polylactide Microspheres by Dispersion Polymerization Using a Polymeric Stabilizer with Hydroxy Groups

Monodisperse poly(D ,L ‐lactide) (PDLLA) microspheres have been prepared by dispersion polymerization of D ,L ‐lactide with a synthetic polymeric stabilizer. The polymerization is carried out in xylene/heptane (1:2, v/v) at 368 K for 3 h with poly[(dodecyl methacrylate)‐co‐(2‐hydroxyethyl methacrylate)] (P(DMA‐co‐HEMA)). P(DMA‐co‐HEMA) has hydroxy groups as an initiation group for pseudoanionic dispersion polymerization. The particle diameter and the coefficient of variation concerning the diameter distribution of the obtained PDLLA microspheres are 3.9 µm and 4.3%, respectively. In addition, from the results of dynamic light scattering measurements, it is found that P(DMA‐co‐HEMA) and the PDLLA‐grafted copolymer form a micellar structure in solution.

     

Effect of reaction parameters on the dispersion polymerization of 1‐vinyl‐2‐pyrrolidone

Nonporous hydrogel microspheres 0.1–1.3 μm in diameter were prepared by the dispersion copolymerization of 1‐vinyl‐2‐pyrrolidone and ethylene dimethacrylate as a crosslinking agent. The crosslinking was evidenced by solid state ¹³C NMR and elemental analysis. The effect of various parameters including selection of solvent (cyclohexane, butyl acetate), initiator (4,4′‐azobis(4‐cyanopentanoic acid), 2,2′‐azobisisobutyronitrile, dibenzoyl peroxide) and stabilizer on the properties of resulting microspheres has been studied. Dynamic light scattering and photographic examination were used for determination of the diameter and polydispersity of microspheres. Increasing concentration of steric stabilizer in the initial polymerization mixture decreased the particle size. The particle size depended on the molecular weight of polystyrene‐block‐hydrogenated polyisoprene stabilizer, but not on the number of PS and polybutadiene blocks in the styrene–butadiene block copolymer stabilizers. Dibenzoyl peroxide used as an initiator resulted in agglomeration of particles. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 653–663, 2000     

Surface treatment and biomimetic mineralization of porous microspheres fabricated by calcium gluconate-<Emphasis Type="Italic">g</Emphasis>-poly(D,L-lactide)

Porous hybrid microspheres were fabricated by the synthesized calcium gluconate-g-poly(D,L-lactide) (CG-g-PDLLA) composites. These hybrid microspheres were treated with an alkaline solution for different period of time to control the amount of generated carboxylate groups and remained CG on the surface. The microspheres were then incubated in a supersaturated simulated body fluid (1.5 SBF) solution for different time to investigate their biomimetic mineralization behavior. The depositions were found to have a fine cluster morphology, a similar crystal structure and chemical structure to natural hydroxyapatite, and a medium Ca/P of approximately 1.30. The effect of surface treating time on the structure and mineralization behavior of these microspheres has been discussed in detail. The results indicate that the nucleation and growth of apatite on the surface are influenced by the induced carboxylate groups and the remained CG. The hybrid CG-g-PDLLA microspheres have the potential as a novel alternative in bone tissue engineering.     

Stabilizer‐free dispersion copolymerization of maleic anhydride and vinyl acetate. I. Effects of principal factors on microspheres

A novel dispersion copolymerization of maleic anhydride (MAn) and vinyl acetate (VAc) without adding stabilizer is developed, which gives uniform copolymer microspheres with tunable sizes. Some principal factors affecting the microspheres, such as reaction time, monomer concentration and feed ratio, reaction media, and cosolvent, were investigated. It was found that the stabilizer‐free dispersion copolymerization of MAn and VAc is a rapid process, and the particle size grows in accordance with the evolution of polymerization. The chemical composition of the copolymer microspheres was characterized by FT‐IR and ¹³C NMR spectroscopies. Over a wide range of monomer concentrations, the microspheres can always be formed and stably dispersed, with uniform sizes ranging from 180 nm to 740 nm. The yield of copolymer microspheres reaches a maximum at 1:1 feed ratio of MAn to VAc, owing to the alternating copolymerization between the binary monomers by a known charge‐transfer‐complex mechanism. However, the diameter of microspheres drastically increases when MAn content is enhanced. Only some specific alkyl ester solvents, such as n‐butyl acetate, isobutyl acetate, n‐amyl acetate, are desirably fit for this unique stabilizer‐free dispersion polymerization. Furthermore, we found that when some acetone is added as a cosolvent, the copolymer microspheres can still be formed, with much larger diameters. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3760–3770, 2005     

Preparation of monodisperse polystyrene microspheres: effect of reaction parameters on particle formation,and optical performances of its diffusive agent application

There are three monodisperse polystyrene (PSt) microspheres, 1.10, 3.13, and 5.21 um in diameter were prepared by dispersion polymerization in ethanol/iso-propanol media. 2,2′-azobis(isobutyronitrile) (AIBN) and poly(acrylic acid) (PAA) were utilized as initiator and steric stabilizer, respectively. The effects of the PAA stabilizer, AIBN initiator, St monomer, and EtOH solvent on particle size and size distribution were reviewed in this article. Besides, optical properties including total transmittance (T%) and transmittance haze (H%) were performed when these three monodisperse PSt microspheres were applied as diffusive agents. The results were examined in terms of total interface area in a system, and came up an optimal situation between transmittance haze (H _max% = 65%) and T% when total surface area of particles is around 45,000 cm².     

Synthesis of monodisperse polystyrene microspheres by dispersion polymerization using sodium polyaspartate

We prepared monodisperse polystyrene microspheres by dispersion polymerization using sodium polyaspartate (PAspNa) as a dispersion stabilizer in an ethanol/water medium. The influence of reaction parameters, i.e., the volume fraction of ethanol in the medium, stabilizer concentration, and the monomer concentration, on the average diameter of the prepared polystyrene microspheres and its distribution were investigated. Polystyrene microspheres were successfully prepared, and the average diameter of the prepared monodisperse polystyrene microspheres was controlled by adjusting the reaction parameters. The zeta potential of the microspheres and the time course of conversion, the particle diameter and its distribution, and particle numbers were also examined. It was found that PAspNa as a dispersion stabilizer provides an environmentally benign process for the preparation of monodisperse polymer microspheres by dispersion polymerization.     

Effects of dispersion stabilizer and reaction solvent on forming monodisperse polystyrene microspheres by dispersion polymerization

We used poly(aspartic acid) (PAsp) synthesized by ion exchange with sodium polyaspartate (PAspNa) as a dispersion stabilizer. PAsp improved the dispersion stability and the solubility in the medium for dispersion polymerization. The effects of the stabilizer hydrophobicity on particle formation, conversion, particle diameter, and its distribution of polystyrene microspheres were investigated by using both biodegradable polymers as a dispersion stabilizer. According to these results, we concluded that the polymerization rate of the styrene with PAsp was higher than that of styrene with PAspNa. That is why, smaller and more monodisperse microspheres were prepared with PAsp, compared to those with PAspNa.     

Synthesis and drug controlled release of block copolymers of poly(l-lactide) with poly(d,l-lactide) and related monomers

Four types of new biodegradable block copolymers AB, ABA, AC and AD, where A is poly(L-lactide) (PLLA), B is poly(D, L-lactide) (PDLLA), C is poly(p-dioxanone) (PDON) and D is poly(ϵ-caprolactone) (PCL) with different block lengths were synthesized and characterized by GPC, IR, ¹H-NMR and DSC. There are phase-separated and biodegradable block copolymers. Their in vitro biodegradation rates with the change of composition ratio were studied as well as the biodegradation rates of homopolymers with the series as PDON > PDLLA > PLLA in parallel with their crystallinities, i.e. from amorphous to semicrystalline. All these block copolymers were used as matrix to test their controlled release behavior of levo-norgestrel (LNG) in the form of microspheres through solvent evaporation preparation with thoroughly long-time washing to minimize the generally occurring bursting effect. As a result all of them showed almost constant rate of release even from the initial stage,     

Hydrolyzed Vinyl Acetate–Divinylbenzene Copolymer Microspheres Containing L -Proline for Chiral Separation of Amino Acids

A new packing material for ligand-exchange chromatography, L -proline-modified hydrolyzed vinyl acetate-divinylbenzene copolymer microspheres, has been prepared and evaluated. The microspheres, prepared by a one-step swelling and polymerization method, have a narrow bead size (as determined by scanning electron microscopy, SEM), a broad pore-size distribution (by nitrogen adsorption) and, especially, inhomogeneous structural composition (by differential scanning calorimetry). The support, which has an L -proline content of 0.35 mmol g^–1 (nitrogen analysis), provides good enantioselectivity and column efficiency. Twenty-three of the twenty-four common D ,L -amino acids tested were resolved on a 250 mm × 4.6 mm i.d. column and mixtures of up to seven racemic amino acids were easily separated into their enantiomers. Two average pore diameters, volume-average (d_v) and surface-average (d_s) pore diameters, are defined. The ratio d_v/d_s is used to characterize the broadness of the pore-size distribution. It is shown that the widely used formula d=4V_p/S for cylindrical pores, where V_p is pore volume and S the specific surface area, gives the surface-average pore diameter.     

Photoinitiated dispersion polymerization of methyl methacrylate: A quick approach to prepare polymer microspheres with narrow size distribution

Photoinitiated dispersion polymerization of methyl methacrylate was carried out in a mixture of ethanol and water as dispersion medium in the presence of poly(N‐vinylpyrrolidone) (PVP) as the steric stabilizer and Darocur 1173 as photoinitiator. 93.7% of conversion was achieved within 30 min of UV irradiation at room temperature, and microspheres with 0.94 μm number–average diameter and 1.04 polydispersity index (PDI) were obtained. X‐ray photoelectron spectroscope (XPS) analysis revealed that only parts of surface of the microspheres were covered by PVP. The particle size decreased from 2.34 to 0.98 μm as the concentration of PVP stabilizer increased from 2 to 15%. Extra stabilizer (higher than 15%) has no effect on the particle size and distribution. Increasing medium polarity or decreasing monomer and photoinitiator concentration resulted in a decrease in the particle size. Solvency of reaction medium toward stabilizer, which affects the adsorption of stabilizer on the particle surface, was shown to be crucial for controlling particle size and uniformity because of the high reaction rate in photoinitiated dispersion polymerization. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1329–1338, 2008     

Aggregation Behavior of Poly(ethylene glycol)-block-poly (γ-benzyl L-glutamate)-graft-poly(ethylene glycol) Copolymer and its Blends with Poly(γ-benzyl L-glutamate) Homopolymer in Mixed Solvents

Poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate)-graft-poly(ethylene glycol) (PEG-b-PBLG-g-PEG) copolymer was synthesized by the ester exchange reaction of PBLG-block-PEG copolymer with mPEG. The self-association behaviors of PEG-b-PBLG-g-PEG and its blends with PBLG homopolymer in the mixtures of ethanol and dimethylformamide (DMF) were investigated by transmission electron microscopy (TEM), dynamic light scattering (DLS), and viscometry. Effects of the introduction of PBLG homopolymer, the grafting ratio, and the DMF content on the self-association behaviors of PEG-b-PBLG-g-PEG copolymer in the mixtures of ethanol and DMF were mainly researched. It was revealed that PEG-b-PBLG-g-PEG copolymer could self-assemble to form polymeric micelles with a core-shell structure in various shapes from different preparation conditions. The critical micelle concentration (CMC) and the average particle diameter of the micelles formed by PEG-b-PBLG-g-PEG copolymer in the mixed solvents also changed with different preparation conditions.     

Morphological investigation of styrene and acrylamide polymer microspheres prepared by dispersion copolymerization

 The morphology of the styrene and acrylamide copolymer microspheres prepared by dispersion copolymerization in an ethanol/water medium was investigated. The effects of the styrene/acrylamide ratio, ethanol/water ratio and stabilizer concentration on the particle size and size distribution were studied. It was found that the initial solubility parameter of the system was the key factor in the process. The comonomer acrylamide also played an important role in the particle size and size distribution in the presence of cross-linking agent (divinylbenzene). Received: 29 October 1999 Accepted in revised form: 29 November 1999     

Encapsulation of inorganic particles via miniemulsion polymerization. I. Dispersion of titanium dioxide particles in organic media using OLOA 370 as stabilizer

The dispersion of hydrophilic and hydrophobic titanium dioxide (TiO₂) particles in organic media (styrene and cyclohexane) was studied to evaluate the effect of dispersion quality (i.e., size and stability) on the encapsulation efficiencies of subsequent miniemulsion polymerizations. Through screening studies of various block copolymers, OLOA 370 (polybutene–succinimide pentamine) was chosen as the stabilizer for detailed dispersion studies on both types of TiO₂ particles. As a result of strong interactions between the amine end group of the OLOA 370 stabilizer and the hydroxyl groups on the surface of the hydrophilic TiO₂ particles, a good dispersion stability and small particle size (D_v = 39–45 nm) was obtained using 1.0 wt % stabilizer and 20 min of sonification. The dispersions of the hydrophobic TiO₂ particles resulted in a larger average particle size (D_v = 60 nm) and poorer stability. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4419–4430, 2000     

A Novel,Facile Method for the Preparation of Uniform,Reactive Maleic Anhydride/Vinyl Acetate Copolymer Micro‐ and Nanospheres

Summary: A novel, stabilizer‐free dispersion polymerization with alkyl esters as reaction media gives uniform alternating microspheres of maleic anhydride (MAn)/vinyl acetate (VAc) copolymer. The diameter of the copolymer microspheres could be precisely controlled from 80 to 750 nm by changing the monomer concentration or feed ratio. Moreover, this new type of copolymer microspheres with reactive anhydride groups on the surface has good solubility in common nontoxic solvents such as water and ethanol.

SEM image of the powder surface of copolymer microspheres formed at [MAn] = [VAc] = 1.5 M .     

mPEG-PLA共聚物胶束对DHA的增溶及光保护作用

以聚乙二醇单甲醚(mPEG)和外消旋丙交酯(D,L-LA)为原料,采用开环聚合法合成聚乙二醇单甲醚-聚乳酸(mPEG-PLA)共聚物,并用溶剂挥发法制备包载双氢青蒿素(DHA)的共聚物胶束(DHA/mPEG-PLA)。利用红外光谱(FT-IR)、核磁共振氢谱(1 H-NMR)和接触角测量仪研究了共聚物的结构和性质;利用激光粒度分析仪和扫描电镜(SEM)研究了胶束的粒径和形貌。结果表明mPEG-PLA共聚物的临界胶束浓度(CMC)为7.71mg/L。DHA/mPEG-PLA共聚物胶束呈球形,平均粒径(118.1±1.9)nm,载药量和包封率分别为(2.7±0.1)%和(77.1±0.3)%。胶束对DHA的水相表观溶解度增大约1.5倍。紫外光光照39h,纯DHA在混悬液中降解率达37%且持续增长,胶束中DHA降解率达到10%后基本保持不变。     

聚二乙烯基苯微球的合成及其表征研究

采用分散聚合方法制备了聚二乙烯基苯微球 ,研究了引发剂、稳定剂、单体 溶剂比例和溶剂种类对微球粒径及其分布的影响 ,在适当的条件下可以得到平均粒径较大、粒径分布较窄的微球 .用红外光谱法研究了聚合物微球内稳定剂、悬挂双键以及对位和间位二乙烯基苯含量随聚合过程的进行发生的变化 .测得的微球TG曲线表明 ,聚合物微球具有良好的热稳定性 .     

Preparation of polymer microspheres from solutions

Polymer microspheres are obtained by the dropwise addition of a precipitant, containing a polymeric stabilizer, into a polymer solution, containing a polymeric stabilizer. The polymer and stabilizer concentrations, the stirring speed, and the precipitation temperature determine the size and size uniformity of the microspheres. Seven polymer microspheres of polyimide, poly(ether imide), poly(ether ketone), poly(phenylene oxide), polysulfone, poly(vinylidene fluoride), and cellulose diacetate have been prepared with dimethylacetamide as the solvent, with water as the precipitant, and with poly(vinyl alcohol) as the stabilizer. The size and size uniformity of the obtained microspheres are d = 2.3–25.7 μm and ? = 0.15–0.50, respectively (? = σ/d, where ? is the dispersion coefficient, d is the average diameter, and σ is the standard deviation of the diameter). © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 159–165, 2003     

Controlled polymerization of ϵ-caprolactone -from macromolecules to microspheres

Pseudoanionic polymerization of ϵ-caprolactone (CL), initiated with dialkylaluminum alkoxides, was used for the tailored synthesis of poly(CL) with M̄_n ≤ 100 000 and M̄_w /M̄_n < 1. 20. Macromolecules with functional groups at one or at both ends were obtained in this way. Controlled polymerization of CL allowed to prepare poly(dodecyl acrylate)-g-poly(ϵ-caprolactone) (poly(DAC)-g-poly(CL)) with well defined poly(CL) grafts. These copolymers were used as the surface active agents for the direct synthesis of poly(CL) microspheres. The number average diameter (D̄_n ) of poly(CL) microspheres varied from 0.628 μm to 0.94 μm and the diameter polydispersity (D̄_v /D̄_n ) varied from 1.038 to 1.26, depending on the composition of poly(DAC)-g-poly(CL). Human serum albumin (HSA) and human gamma globulins (_γ G) were attached to the poly(CL) microspheres. The maximal surface concentrations of HSA and _γ G adsorbed onto the microspheres were equal to 9·10⁻⁴ g/m² and 2.0·10⁻³ g/m² respectively.