Preparation and in vitro release behavior of urapidil hydrochloride loading into microspheres based on poly(L‐lactide)

Microencapsulation of the antihypertensive drug urapidil hydrochloride was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Poly(L ‐lactide) (PLLA) microspheres were prepared using an alternative oil‐in‐water (O/W) solvent‐evaporation method such as the O/W cosolvent solvent‐evaporation method and O/W with various electrolytes added to the aqueous phase method. The surface morphology and the size of the microspheres were observed by scanning electron microscope. Meanwhile, the drug loading efficiency of microspheres and the in vitro release of urapidil hydrochloride from microspheres were performed. The release study indicated that the urapidil hydrochloride‐PLLA microspheres exhibited better sustained release capacity, and the kinetics of urapidil hydrochloride‐PLLA microspheres in vitro release could be described by the Higuchi equation. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and characterization of star‐shaped PLLA with sorbitol as core and its microspheres application in controlled drug release

The purpose of this study was to investigate the suitability of a six‐arm star‐shaped poly(l ‐lactide)s (s‐PLLA) as controlled drug carriers for hydrophobic drug molecules. First, s‐PLLA was synthesized by ring‐opening polymerization of l ‐lactide using sorbitol as initiator and stannous octoate as catalyst. The structure and molecular weight (M_w) of s‐PLLA was characterized with ¹H NMR, ¹³C NMR, and GPC. Second, rifampicin (RIF) used as a model drug was encapsulated within the microspheres of s‐PLLA via oil‐in‐water emulsion/solvent evaporation technique. The morphology, drug encapsulation efficiency (EE), and in vitro release behavior of the prepared microspheres were studied in details. Results indicated that the average diameters of s‐PLLA microspheres can be controlled between 8 and 20 µm by varying the copolymer's concentration or M_w . The EE of RIF was mainly determined by the concentration of s‐PLLA. The in vitro study showed that the burst release behavior can be depressed by increasing the M_w of the s‐PLLA. Present work suggests that the synthesized s‐PLLA could be used as a new material for drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42213.     

Preparation of porous poly(L‐lactic acid)‐co‐(trimethylene‐carbonate) structures using supercritical CO2 as antisolvent and as foaming agent

In this work, porous structures of poly(l ‐lactic acid)‐co‐(tri‐methylene‐carbonate) (PLLA‐co‐TMC) were successfully fabricated using two experimental methods, that is, using supercritical CO₂ as antisolvent and as foaming agent through the pressure induced phase separation technique. Considering the phase inversion method, the effect of the initial polymer concentration of the solution, pressure, and temperature on the morphology of the final porous structure (pore size, porosity, and cell density) was investigated. The L–L demixing process was suggested as the dominant mechanism for the phase separation and pore production. The temperature window, for which PLLA‐co‐TMC porous structures are successfully produced using the pressure induced phase separation technique, was determined at 150 and 210 bar. The effect of temperature on the final porous structure was investigated. POLYM. ENG. SCI., 57:1005–1015, 2017. © 2016 Society of Plastics Engineers     

A physical route to porous ethyl cellulose microspheres loaded with TiO2 nanoparticles

Porous ethyl cellulose (EC) microspheres were prepared via a physical method in oil‐in‐water (O/W) emulsions. The morphologies and pore structures of the resulting porous microspheres were investigated by scanning electron microscopy (SEM), mercury porosimeter and spectrometer equipped with an integrating sphere. The increase of EC amount in oil phase will increase the size of the microspheres. All the microspheres possess open macropores in the shell and interconnected pores inside the microspheres by means of phase separation. The saturation of the Ethyl acetate (EA) in external phase has an effect on the morphology of the EC particles obtained. Using EA unsaturated aqueous solution as the external water phase in the emulsion process results in the formation of porous EC particles with irregular shape. The loaded TiO₂ nanoparticles uniformly disperse in EC matrix, and slightly deceases the size and volume of interconnected pores inside the microspheres. The addition of TiO₂ nanoparticles is also proved to increase the light‐scattering power of the porous EC microspheres. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40822.     

Preparation of poly(acrylamide‐co‐acrylic acid)/silica nanocomposite microspheres and their performance as a plugging material for deep profile control

In this work, poly(acrylamide‐co‐acrylic acid)/silica [poly(AM‐co‐AA)/SiO₂] microspheres were prepared by inverse phase suspension polymerization in the presence of γ‐3‐(trimethoxysilyl) propyl methacrylate (or 3‐methacryloxypropyltrimethoxysilane) modified SiO₂. The effects of SiO₂ nanoparticles on tuning morphology and properties of the nanocomposite microspheres were studied. Plugging ability and oil displacement performance were also systematically investigated by single‐ and double‐tube sand pack models. The results showed that SiO₂ nanoparticles can effectively adjust surface smoothness, swelling behavior, and thermal stability of the nanocomposite microspheres. Compared with pure copolymer microspheres, these nanocomposite microspheres also displayed better salt tolerance and shear resistance. Such multifunctional nanocomposite microspheres can provide effective plugging in the high‐permeability channels and can also achieve deep profile control. The highest plugging rate can be 86.11% and the oil recovery for low‐permeability tube was enhanced by 19.69%. This research will provide a candidate material for the further enhanced oil recovery (EOR) research and supply the theoretical support for profile control system in field application. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45502.     

Porous biodegradable polyester blends of poly(L‐lactic acid) and poly(ε‐caprolactone): physical properties,morphology, and biodegradation

Poly(L ‐lactic acid) (PLLA), poly(ε‐caprolactone) (PCL), and their films without or blended with 50 wt% poly(ethylene glycol) (PEG) were prepared by solution casting. Porous films were obtained by water‐extraction of PEG from solution‐cast phase‐separated PLLA‐blend‐PCL‐blend‐PEG films. The effects of PLLA/PCL ratio on the morphology of the porous films and the effects of PLLA/PCL ratio and pores on the physical properties and biodegradability of the films were investigated. The pore size of the blend films decreased with increasing PLLA/PCL ratio. Polymer blending and pore formation gave biodegradable PLLA‐blend‐PCL materials with a wide variety of tensile properties with Young's modulus in the range of 0.07–1.4 GPa and elongation at break in the range 3–380%. Pore formation markedly increased the PLLA crystallinity of porous films, except for low PLLA/PCL ratio. Polymer blending as well as pore formation enhanced the enzymatic degradation of biodegradable polyester blends. Copyright © 2006 Society of Chemical Industry     

Mesoporous water adsorbent material from poly high internal phase emulsion for agriculture application

Mesoporous water adsorbent materials were prepared by high internal phase emulsion (HIPE) technique: a technique which used aqueous phase (water phase) as a temporary template (in the form of droplets) and oil phase (polymer phase) as a continuous structure. This research describes the preparation of porous poly[S/ethylene glycol dimethylacrylate (EGDMA)]HIPE from styrene crosslinked with EGDMA. Effects of chemical composition on the pores of the mesoporous adsorbents were investigated. The EGDMA concentration was varied between 0 and 40% of oil phase by total volume to give polyHIPE with various amounts of hydroxyl groups. Effects of oil: aqueous phase ratio on mesoporous adsorbent polyHIPEs resulted in interconnected pores in their morphology. The EGDMA concentration also affected the obtained polyHIPE morphology. The water adsorption of poly(S/EGDMA)HIPE gave high water adsorption, up to 350% of dry weight. The obtained polyHIPE with large average pore size were also found to give high water adsorption capacity. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45509.     

Hollow porous poly(lactic acid) microspheres

On the basis of the water solubility of poly(N‐vinyl‐2‐pyrrolidinone), hollow porous poly(lactic acid) microspheres (HPPLAs) were prepared by a water‐in‐oil‐in‐water multiple‐emulsion solvent evaporation method. The influence of the concentration of the stabilizer Span80 in the oil phase on the morphology was investigated. It was found that when the content of Span80 solutions was 3.5 wt %, most HPPLAs were about 2 μm in diameter. Field scanning electron microscopy results show that the HPPLAs were porous and hollow. The structure and crystal form of the HPPLAs were characterized by Fourier transform infrared spectroscopy and X‐ray diffraction analysis. Using these HPPLAs as degradable templates, we successfully synthesized Litchi‐like polystyrene (PS) microspheres about 2 μm in diameter by the emulsion method. When used as drug carriers, these HPPLAs would be convenient in which to embed drugs, whereas the Litchi‐like PS microspheres may have potential as new materials for polymer modification. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

How to circumvent untoward drug crystallization during emulsion‐templated microencapsulation process

Unwanted drug crystals often form on the surface of PLGA microspheres or in an aqueous phase when a hydrophobic drug undergoes emulsion‐templated microencapsulation processes. In our study, over 70% of progesterone crystallizes in the aqueous phase when microencapsulation proceeds with a typical oil‐in‐water solvent evaporation process. During filtration employed for microsphere recovery, unentrapped drug crystals are collected alongside with progesterone‐containing microspheres. This phenomenon accompanies unfavorable consequences on the microsphere quality. In contrast, when microspheres are prepared with a new solvent extraction‐evaporation hybrid process, it is possible to completely avoid drug crystallization. Consequently, the new microencapsulation technique yields high drug encapsulation efficiencies of ≥ 90.8%, and the resultant microspheres show a homogeneous size distribution pattern. Also, the microsphere surface is free of drug crystals. For loading hydrophobic drugs into PLGA microspheres, the new microencapsulation process reported in this study has distinct advantages over commonly used emulsion‐templated solvent evaporation processes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43768.     

Electrospun fibers of poly(l‐lactic acid) containing lovastatin with potential applications in drug delivery

Lovastatin (Merck's Mevacor) is a statin drug designed to lower cholesterol, and reduce the risk of heart attack and stroke. We use electrospinning to combine the biomedical properties of lovastatin with the advantages of electrospun fibers to prepare a composite biomaterial for lovastatin delivery. Poly(l ‐lactic acid) (PLLA), a biodegradable and biocompatible polymer, was co‐spun with lovastatin. Incorporation of lovastatin at 5 or 10 wt % improved fiber alignment and surface smoothness, and increased fiber diameter. Influence of lovastatin on the phase structure (crystal, mobile amorphous, and rigid amorphous fractions) was investigated using scanning calorimetry and synchrotron X‐ray scattering. Addition of lovastatin resulted in increased crystallinity and reduced mobile amorphous fraction. PLLA fibers were characterized in terms of their drug release kinetics in comparison to PLLA film. High drug entrapment efficiency (ranging from 72% to 82%) and appropriate release profiles were achieved. In vitro drug release studies demonstrated that release occurred in two stages: an initial rapid release over the first day and a slower second stage of release which approached a plateau after 7 days. PLLA fibers have a higher release rate than comparable film. Electrospun biomaterial fibers of PLLA provide a promising new release strategy for delivery of lovastatin. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45287.     

Crystallization behavior,heat resistance,and mechanical performances of PLLA/myo‐inositol blends

In this work, use of myo‐inositol as a biobased nucleating agent (NA) for PLLA was researched. Effects of myo‐inositol on non‐isothermal and isothermal crystallization behaviors of PLLA at temperatures ranged from 85 °C to 130 °C were studied by using DSC, POM and WAXD. Isothermal crystallization kinetics results showed that the incorporation of myo‐inositol enhanced significantly the crystallization rate of the PLLA samples. It was confirmed that the optimum isothermal crystallization temperature range was 100 to 110 °C. The above results were instructive to confirm proper heat treatment time and temperature for compression or injection molding to fabricate highly crystallized PLLA articles. The relations among heat treatment time, crystallinity, heat resistance, and mechanical performances of the neat PLLA and PLLA/1% myo‐inositol specimens prepared by compression molding were investigated. Compared with the PLLA specimens, the PLLA/1% myo‐inositol specimens showed a shorter heat treatment time to reach the maximum crystallinity. Vicat softening temperature, as well as tensile strength, modulus, and toughness of the PLLA/1% myo‐inositol specimens was improved when crystallinity increased from 5.4% to 38.1%. Considering the nontoxicity and biocompatibility of myo‐inositol, PLLA/myo‐inositol blends would be potential to prepare some products, which are required higher health standard and can be used in elevated temperature environments. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44732.     

Biodegradable polymeric injectable implants for long‐term delivery of contraceptive drugs

Development of injectable, long‐lasting, contraceptive drug delivery formulations, and implants are highly desired to avoid unplanned pregnancies while improving patient compliance and reducing adverse side effects and treatment costs. The present study reports on the fabrication and characterization of two levonorgestrel (LNG) microsphere injectable formulations. Poly(?‐caprolactone) (PCL) with 12.5% and 24% (w/w) LNG were fabricated into microspheres, measuring 300 ± 125 µm, via the oil‐in‐water (o/w) emulsion solvent evaporation technique. Formulations showed sustained drug release up to 120 days. FTIR, XRD, DSC, and TGA confirmed the absence of LNG chemical interaction with PCL as well as its molecular level distribution. The in vitro release of LNG was calculated to be Fickian diffusion controlled and properly characterized. The inclusion of multiple elevated release temperatures allowed for the application of the Arrhenius model to calculate drug release constants and representative sampling intervals, demonstrating the use of elevated temperatures for accelerated‐time drug release studies. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46068.     

Effect of composition on morphology structure and cell affinity of poly(caprolactone‐co‐glycolide)‐co‐poly(ethylene glycol) microspheres

Poly(caprolactone‐co‐glycolide)‐co‐poly(ethylene gylcol) copolymers (PCEG) with various composition were synthesized by copolymerization of GA, CL, and PEG. PCEG microspheres were fabricated by oil‐in‐water (o/w) emulsion and solvent‐evaporation technique. Effect of chemical composition on hydrophilicity, crystallinity, and degradation of the PCEG was investigated. It was demonstrated that morphology structure of the microspheres was greatly influenced by chemical composition and hydrophilicity of the PCEG polymer. PCEG microspheres could change from a smooth structure to a regular porous structure and an irregular structure. Moreover, the pore size of them increased with increment of PEG content and length. Cell attachment and growth on the PCEG microspheres were evaluated by using mouse NIH 3T3 fibroblasts as model cells in vitro. The result showed that the PCEG microspheres with large porous structure were more favorable for cell attachment and growth. Thus the PCEG microspheres with rapid degradation rate and large porous structure possess potential use as injectable scaffolds in tissue engineering. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 132, 42861.     

Preparation of Magnetic Porous Microspheres and Their Ability to Remove Oils

Magnetic, porous poly (tripropylene glycol diacrylate) (PTPGDA) microspheres are successfully prepared using a combination of microfluidic emulsification and free‐radical polymerization. The porous structure can be precisely controlled by controlling the amount of the oil‐phase emulsifier polyglycerol polyricinoleate (PGPR). The effects of PGPR content and pH on the contact angle of the microspheres is investigated. The contact angle of the microspheres increases with the raise of PGPR content, and the hydrophobicity of the microspheres remains stable at different pHs. The microstructure, magnetic properties, and oil adsorption abilities of the microspheres are also studied. The as‐prepared microspheres perform adsorption well, the higher the PGPR content, the more pore structures and larger contact angle occurres on the microspheres, which improves the adsorption capacity. In addition, the adsorption capacity of the microspheres for diesel can reach 3.38 g·g^?1 when the mass fraction of PGPR in oil phase is 50% w/v. After adsorbing oil, the microspheres can be separated, recovered, and reused by applying an external magnetic field. The magnetic microspheres have good oil adsorption abilities and recyclability, which shows their potential for use in oil removal.     

Fabrication and surface characterization of electrosprayed poly(L‐lactide) microspheres

Electrospraying is a one‐step technique for fabricating polymeric microspheres/nanospheres, and the surface characterization of polymeric microspheres fabricated under high voltage is different from an emulsion method. In this study, biodegradable poly(l ‐lactide) (PLLA) microspheres were successfully fabricated by electrospraying, and electrospraying parameters were used to investigate the size and ζ potential of the electrosprayed PLLA microspheres. The results demonstrate that electrospraying was a one‐step method for fabricating monodispersed PLLA microspheres with a size of 1.92 ± 0.35 μm and that the enrichment of methyl groups on the surface of the microspheres contributed to the strong hydrophobicity of electrosprayed PLLA microspheres. Of all the electrospraying parameters investigated, the size and ζ potential of the PLLA microspheres increased with increasing solution concentration and flow rate and decreased with increasing injection voltage and collecting distance. The results provide a theoretical basis for preparing electrosprayed polymeric microspheres as drug carriers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Modified poly(L-lactic acid) microspheres with nanofibrous structure suitable for biomedical application

Aminolyzed poly(L-lactic acid) (EPLA) microspheres with nanofibrous structure were prepared for the first time by aminolysis combined with emulsion and thermally induced phase separation technique from a ternary ethylenediamine aqueous solution/poly(L-lactic acid) (PLLA)-dioxane/propanetriol system. The results indicated that ethylenediamine concentration, aminolyzing time, and ratio of dioxane to ethylenediamine in aqueous solution significantly influenced the morphology and structures of microspheres. Under optimum conditions, monodispersed microspheres with nanofibrous structure were obtained. The in vitro bioactivity test showed that EPLA nanofibrous microspheres exhibited a strong apatite-formation ability compared with unmodified PLLA microspheres without nanofibrous structure, indicating that the bioactivity of PLLA microspheres was significantly improved through aminolysis reaction with ethylenediamine.     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Electrospinning of porous polylactic acid fibers during nonsolvent induced phase separation

In this study, porous micron‐sized fibers of polylactic acid (PLA) are fabricated via electrospinning of PLA‐dichloromethane (DCM)‐hexane systems with no post treatment involved. Several compositions from the liquid‐liquid phase separated region of the phase diagram of this ternary system are selected and their electrospinnability are investigated throughout their phase separation process before gelation. We show that under constant processing and ambient parameters, there is a phase separation shelf time for each composition wherein the viscoelasticity of the systems is optimum to produce long, uniform porous fibers. For the first time, we investigate the effect of aging time during phase separation on the morphology of the electrospun fibers using scanning electron microscopy (SEM). Based on our results, certain phase separated systems provide a range of viscosity allowing for the production of porous spherical micro beads or fibers via electrospraying and electrospinning, respectively. It is also shown that obtaining long, uniform fibers from electrospinning of highly phase separated systems, e.g., a gel, is not feasible due to the high degree of crystallinity of their polymer‐rich domains and the solid‐like yielding behavior. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44862.     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres with a controllable particle size based on a composite emulsion and their release properties for curcumin loading

Because of their unique magnetic features and good biocompatibility, magnetic poly(lactic‐co‐glycolic) acid (PLGA) microspheres have great application potential in magnetic targeted drug‐delivery systems. In this research, magnetic PLGA microspheres with controllable particle sizes were successfully prepared from a composite emulsion with a T‐shaped microchannel reactor. A water‐in‐oil‐in‐water composite emulsion was generated by the injection of a dichloromethane/gelatin water‐in‐oil initial emulsion into the microchannel together with a coating aqueous phase, that is, the aqueous solution of glucose and poly(vinyl alcohol). The mean particle size of the microspheres could be controlled by the manipulation of the osmotic pressure difference between the internal and external aqueous phases via changes in the glucose concentration. Curcumin, a drug with an inhibitory effect on tumor cells, was used to exemplify the release properties of the magnetic PLGA microspheres. We found that the mean particle size of the microspheres ranged from 16 to 207 μm with glucose concentrations from 0 to 20 wt %. The resulting microspheres showed a rapid magnetic response, good superparamagnetism, and a considerable magnetocaloric effect, with a maximum magnetic entropy of 0.061 J·kg^?1·K^?1 at 325 K. An encapsulation efficiency of up to 77.9% was achieved at a loading ratio of 3.2% curcumin. A release ratio of 72.4% curcumin from the magnetic PLGA microspheres was achieved within 120 h in a phosphate‐buffered solution. The magnetic PLGA microspheres showed potential to be used as drug carriers for magnetic targeted tumor therapy. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43317.     

Enhanced crystallization rate and mechanical properties of poly(l‐lactic acid) by stereocomplexation with four‐armed poly(ϵ‐caprolactone)‐block‐poly(d‐lactic acid) diblock copolymer

Poly(l ‐lactic acid) (PLLA) was blended with a series of four‐armed poly(? ‐caprolactone)‐block ‐poly(d ‐lactic acid) (4a‐PCL‐b ‐PDLA) copolymers in order to improve its crystallization rate and mechanical properties. It is found that a higher content of 4a‐PCL‐b ‐PDLA copolymer or longer PDLA block in the copolymer lead to faster crystallization of the blend, which is attributed to the formation of stereocomplex crystallites between PLLA matrix and PDLA blocks of the 4a‐PCL‐b ‐PDLA copolymers. Meanwhile, the PDLA block can improve the miscibility between flexible PCL phase and PLLA phase, which is beneficial for improving mechanical properties. The tensile results indicate that the 10% 4a‐PCL_5k‐b ‐PDLA_5k/PLLA blend has the largest elongation at break of about 72% because of the synergistic effects of stereocomplexation between enantiomeric PLAs, multi‐arm structure and plasticization of PCL blocks. It is concluded that well‐controlled composition and content of 4a‐PCL‐b ‐PDLA copolymer in PLLA blends can significantly improve the crystallization rate and mechanical properties of the PLLA matrix. © 2017 Society of Chemical Industry