Thermoresponsive hollow magnetic microspheres with hyperthermia and controlled release properties

Thermoresponsive hollow magnetic microspheres consisting of a hollow magnetic core, a carbon shell, and a smart polymer layer are presented in this article. A carbon nanomaterial was used as a steric stabilizer for Fe₃O₄ nanoparticles and a supporter for polymer. The thermoresponsive monomer, N‐isopropyl acrylamide, was grafted on the carbon‐encapsulate hollows by surface radical polymerization. The experimental results indicate that the composites had a phase‐transition temperature around 43°C and a saturation magnetization of 56.9 emu/g; this showed apparent thermosensitivity and magnetism. The performances in hyperthermia evaluated by an inductive magnetic field showed that the hybrid microspheres had a specific absorption rate of 240 W/g. The model drug, 5‐fluorouracil, was loaded in and released from the microspheres with different release rates at 35 and 50°C. This demonstrated that the as‐synthesized microspheres had a thermotriggered release ability and would be a good drug carrier in the biomedical field. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42617.     

Preparation and characterization of a positive thermoresponsive hydrogel for drug loading and release

A positive thermoresponsive hydrogel composed of poly(acrylic acid)‐graft‐β‐cyclodextrin (PAAc‐g‐β‐CD) and polyacrylamide (PAAm) was synthesized with the sequential interpenetrating polymer network (IPN) method for the purpose of improving its loading and release of drugs. The structure and properties of the PAAc‐g‐β‐CD/PAAm hydrogel (IPN hydrogel) were characterized with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and swelling measurements. FTIR studies showed that the IPN hydrogel was primarily composed of an IPN of PAAc‐g‐β‐CD and PAAm. The data from DSC and swelling measurements indicated that the phase‐transition temperature or upper critical solution temperature (UCST) of the IPN hydrogel was approximately 35°C. Through the measurement of the temperature dependence of the swelling, increases in the UCST and non‐sensitivity to changes in the salt concentration were observed for the IPN hydrogel versus the normal IPN hydrogel poly(acrylic acid)/PAAm (without β‐cyclodextrin). Furthermore, the swelling/deswelling kinetics of the IPN hydrogel also exhibited an improved controllable response rate versus the normal IPN hydrogel. Ibuprofen (IBU) was chosen as the model drug for examining loading and release from the IPN hydrogel. The experimental data proved that the IPN hydrogel provided a positive drug release pattern; the IBU released faster at 37°C than at 25°C, and improved drug loading and controlled release were achieved by the IPN hydrogel versus the normal IPN hydrogel. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Fabrication and drug release properties of poly(5‐benzyloxy‐trimethylene‐co‐glycolide) microspheres

Poly(5‐benzyloxy‐trimethylene carbonate‐co‐glycolide) random copolymers were synthesized through the ring‐opening polymerization of 5‐benzyloxy‐trimethylene carbonate and glycolide (GA). The copolymers with different compositions, PBG‐1 with 17% GA units and PBG‐2 with 45% GA units, were obtained. Using these copolymers, microsphere drug delivery systems with submicron sizes were fabricated using an “ultrasonic assisted precipitation method.” The in‐vitro drug release from these microspheres was investigated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Mechanical properties of block poly(propylene carbonate‐cyclohexyl carbonate) investigated by nanoindentation and DMA methodologies

To extend the practical application of poly(propylene carbonate) (PPC), the chemical methods were used to improve its mechanical properties. In this connection, random copolymer poly(propylene‐cyclohexyl carbonate) (PPCHC) and di‐block copolymers poly(propylene carbonate‐cyclohexyl carbonate) (PPC‐PCHC) were synthesized. Dynamic mechanical analysis (DMA), nanoindentation and nanoscratch test were applied to evaluate their mechanical properties. The storage's modulus, Young's modulus (E) and hardness (H) obtained from DMA and nanoindentation tests showed that the introduction of the third monomer cyclohexene oxide (CHO) can greatly improve the mechanical properties of PPC, and that the block copolymer PPC‐PCHC hand better mechanical properties than the random copolymer PPCHC. The annealing treated PPC‐PCHCs exhibited deteriorated mechanical properties as compared with untreated PPC‐PCHC. From the results of scratch tests, the plastic deformation of PPC‐PCHC was smaller than those of PPC and PPCHC. Meanwhile, the plastic deformations of the heat‐treated PPC‐PCHCs were smaller than the untreated PPC‐PCHC because of the possible rearrangement of the molecular chains of PPC‐PCHC. The scratch hardness (H_s) of the block copolymer PPC‐PCHC is larger than random polymer PPCHC and PPC, but lower than the values of heat‐treated samples indicating that the surfaces' hardness of block polymers increase after heat treatment. These different measurement methodologies provide a more precise assessment and understanding for the synthesized block polymers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and release kinetics of carboxymethyl chitosan/cellulose acetate microspheres as drug delivery system

Carboxymethyl chitosan, a water soluble chitosan derivative, was prepared from chitosan using monochloroacetic acid. Carboxymethyl chitosan/cellulose acetate microspheres (CCM) were prepared using the method of W/O/W and emulsification solvent evaporation as drug delivery system. The CCMs prepared were spherical, free‐flowing, and nonaggregated with the smooth appearance and many small pores on the surface. All CCMs prepared had sustained release efficiency for acetaminophen and the optimal formulation was that carboxymethyl chitosan of 2.0% and 1360 KD. In addition, the release rate of drug from CCMs in dilute hydrochloric acid was much slower than that in phosphate buffer saline (pH 6.8) during 24 h. It is illustrated that the drug loaded in CCMs released slower in simulated gastric fluid than that in simulated intestinal fluid. Furthermore, the drug release data showed better fitness with the first order model which indicated that the drug release from CCMs was depended on the drug concentration in the polymeric networks. And the release of drug from CCMs indicated diffusion‐controlled drug release based on Fickian diffusion and accompanied with anomalous transport (i.e., non‐Fickian diffusion) according to the values obtained from Higuchi model and Peppas models. So it was shown that the CCMs might be an ideal sustained release system for acid‐labile drugs both for the solubility of carboxymethyl chitosan and the release media. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42152.     

Thermally and magnetically dual‐responsive mesoporous silica nanospheres: preparation,characterization, and properties for the controlled release of sophoridine

Novel thermally and magnetically dual‐responsive mesoporous silica nanoparticles [magnetic mesoporous silica nanospheres (M‐MSNs)–poly(N‐isopropyl acrylamide) (PNIPAAm)] were developed with magnetic iron oxide (Fe₃O₄) nanoparticles as the core, mesoporous silica nanoparticles as the sandwiched layer, and thermally responsive polymers (PNIPAAm) as the outer shell. M‐MSN–PNIPAAm was initially used to control the release of sophoridine. The characteristics of M‐MSN–PNIPAAm were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetry, N₂ adsorption–desorption isotherms, and vibrating specimen magnetometry analyses. The results indicate that the Fe₃O₄ nanoparticles were incorporated into the M‐MSNs, and PNIPAAm was grafted onto the surface of the M‐MSNs via precipitation polymerization. The obtained M‐MSN–PNIPAAm possessed superparamagnetic characteristics with a high surface area (292.44 m²/g), large pore volume (0.246 mL/g), and large mesoporous pore size (2.18 nm). Sophoridine was used as a drug model to investigate the loading and release properties at different temperatures. The results demonstrate that the PNIPAAm layers on the surface of M‐MSN–PNIPAAm effectively regulated the uptake and release of sophoridine. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40477.     

Miscibility and properties of completely biodegradable blends of poly(propylene carbonate) and poly(butylene succinate)

Completely biodegradable blends of poly (propylene carbonate) (PPC) and poly(butylene succinate) (PBS) were melt‐prepared and then compression‐molded. The miscibilities of the two aliphatic polyesters, that is, PPC and PBS, were investigated by dynamic mechanical analysis (DMA) and scanning electron microscopy (SEM). The static mechanical properties, thermal behaviors, crystalline behavior, and melt flowability of the blends were also studied. Static tensile tests showed that the yield strength and the strength at break increased remarkably up to 30.7 and 46.3 MPa, respectively, with the incorporation of PBS. The good ductility of the blends was maintained in view of the large elongation at break. SEM observation revealed a two‐phase structure with good interfacial adhesion. The immiscibility of the two components was verified by the two independent glass‐transition temperatures obtained from DMA tests. Moreover, thermogravimetric measurements indicated that the thermal decomposition temperatures (T_?5% and T_?10%) of the PPC/PBS blends increased dramatically by 30–60°C when compared with PPC matrix. The melt flow indices of the blends showed that the introduction of PBS improved the melt flowability of the blends. The blending of PPC with PBS provided a practical way to develop completely biodegradable blends with applicable comprehensive properties. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Fabrication of sustained‐release and antibacterial citronella oil‐loaded composite microcapsules based on Pickering emulsion templates

In this work, the citronella oil (CTO)‐loaded composite microcapsules with hydroxyapatite (HAp)/quaternary ammonium salt of chitosan (HACC)/sodium alginate (SA) shells are facilely and effectively fabricated by templating citronella oil‐in‐water Pickering emulsions, which are stabilized with HAp nanoparticles. The microcapsule composite shells are prepared by the electrostatic adsorption of HACC and SA, and then chelation interaction of alginate and Ca²⁺ ions released from HAp nanoparticles. Scanning electronic microscope observation shows that the microcapsules have a spherical shape. Thereafter, Fourier transform infrared spectroscopy and thermal gravimetric analysis results indicate that CTO is successfully loaded into the microcapsules, and the related CTO‐loaded microcapsules possess the thermal stability. Moreover, the in vitro release study of CTO shows that the microcapsules have sustained release activity, and the related CTO release profiles can be well described by Rigter–Peppas model. The antimicrobial assays of microcapsules display the antibacterial effect of CTO‐loaded microcapsules against Staphylococcus aureus and Escherichia coli. Overall, this study opens up new potentiality for unstable active ingredient as an environmental friendly and ingenious microencapsulation in food and agriculture applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46386.     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.     

Versatile poly(maltose) micro/nanoparticles with tunable surface functionality as a biomaterial

Maltose, a natural disaccharide, was crosslinked with divinyl sulfone to prepare poly(maltose) (p(MAL)) micro/nanoparticles via one step microemulsion system with ≥90% ± 5% yield in a size rage of 0.5–100 μm for the first time. P(MAL) was modified (m-p(MAL)) with ethylenediamine (EDA), polyethyleneimine (PEI), and taurine (TA) to render additional functionalities, that is, amine and sulfate groups. The isoelectronic point of bare p(MAL) particles were calculated at pH 2.2 ± 0.5 and was changed to 1.3 ± 0.5, 4.3 ± 1.0, and 8.1 ± 0.7 for TA (p(MAL)/TA), EDA (p(MAL)/EDA), and PEI (p(MAL)/PEI) modification, respectively. Bare p(MAL) particles were found to be biocompatible up to 2 mg/ml with hemolysis and blood clotting tests, whereas the modified p(MAL) particles were found to be biocompatible at 1 mg/ml concentration. Additionally, it was found that TA- and PEI-modified p(MAL) particles induced blood clotting mechanisms. Sodium diclofenac as model drug was released at proportions of 8.7% ± 1.3%, 3.9% ± 0.2%, 8.8% ± 0.9%, and 31.6% ± 0.4% of the loaded drug in phosphate buffered saline solution from p(MAL), p(MAL)/TA, p(MAL)/EDA, and p(MAL)/PEI, respectively. The inhibition of antimicrobial activity of p(MAL)/PEI particles at 20 mg/ml concentration for Escherichia coli and Staphylococcus aureus strain was determined as 99.86% ± 0.3% and 99.79% ± 0.25%, respectively.     

Synthesis and characterization of a drug‐delivery system based on melamine‐modified poly(vinyl acetate‐co‐maleic anhydride) hydrogel

Three‐dimensional polymeric networks, which quickly swell by imbibing a large amount of water or deswell in response to changes in their external environment, are called hydrogels. These types of polymeric materials are good potential candidates for drug‐delivery systems. In this study, we first synthesized poly(vinyl acetate‐co‐maleic anhydride) by free‐radical copolymerization. Then, they were modified with different molar ratios of melamine to prepare hydrogels that could be used in drug‐delivery systems. The hydrogels were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, differential scanning calorimetry, and scanning electron microscopy. In the second step, Ceftazidime antibiotic was loaded on selected hydrogels. The in vitro drug release was investigated and compared in three different media (HCl solution at pH = 3 and buffer solutions at pH 6.1and pH 8). © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40389.     

Preparation and release study of ibuprofen‐loaded porous matrices of a biodegradable poly(ester amide) derived from L‐alanine units

Scaffolds of a biodegradable poly(ester amide) constituted of L ‐alanine, sebacic acid, and 1,12‐dodecanediol units (abbreviated as PADAS) were prepared by the compression‐molding/particulate‐leaching method. The influence of the type, size, and percentage of salt on the scaffold porosity and morphology was evaluated. The thermal behavior and crystallinity were also studied for samples obtained under different processing conditions. PADAS scaffolds were not cytotoxic because they showed good cell viability and supported cell growth at a similar ratio to that observed for the biocompatible materials used as a reference. The use of PADAS scaffolds as a drug‐delivery system was also evaluated by the employment of ibuprofen, a drug with well known anti‐inflammatory effects. Different drug‐loading methods were considered, and their influence on the release in a Sörensen's medium was evaluated as well as the influence of the scaffold morphology. A sustained release of ibuprofen could be attained without the production of a negative effect on the cell viability. The release kinetics of samples loaded before melt processing was well described by the combined Higuchi/first‐order model. This allowed the estimation of the diffusion coefficients, which ranged between 3 × 10^?14 and 5 × 10^?13 m²/s. Samples loaded by immersion in ibuprofen solutions showed a rapid release that could be delayed by the addition of polycaprolactone to the immersion medium (i.e., the release rate decreased from 0.027 to 0.015 h^?1). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Preparation of a biodegradable poly(vinyl alcohol)–starch composite film and its application in pesticide controlled release

With the herbicide 2,4‐dichlorophenoxyacetic acid (2,4‐D) as a model drug, a series of poly(vinyl alcohol)–starch (PVA–ST) composite films for controlled drug release were prepared by a casting method. The morphology, structure, and release properties were systematically investigated. The results show that when the PVA–ST composite film containing 2,4‐D (PSD) was immersed in water, the drug‐release rate was high, whereas the introduction of sodium montmorillonite (Na‐MMT) and an alginate ion‐crosslinking structure to PSD significantly reduced the release rate and maintained the sustained release of the model drug for a longer period. A leaching experiment through the soil layer showed that the PSD drug‐loaded film with Na‐MMT and the alginate ion‐crosslinking structure (PSDMA) possessed good release properties. The cumulative leached amount of the herbicide 2,4‐D after eight irrigations was reduced to 57.6% from 100%. In addition, the PSDMA film showed favorable mechanical and thermal properties. This composite film is expected to have potential applications in the fields of agriculture, drug delivery, and more. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45051.     

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Preparation of carbon dioxide/propylene oxide/ε-caprolactone copolymers and their drug release behaviors

Summary Poly (propylene-ram-ε-caprolactone carbonate) (PPCL) and poly (propylene carbonate) (PPC) were synthesized by ring-opening copolymerization from carbon dioxide, propylene oxide (PO) and ε-caprolactone (CL) using a polymer-supported bimetallic complexes (PBM) as catalyst. PPC and PPCL microspheres containing a 5-alpha reductase inhibitor, finasteride were elaborated by a conventional oil-in-water (O/W) emulsion-solvent evaporation method. The effects of polymer used on microspheres morphology, size, drug loading, encapsulation efficiency and drug release behaviors were examined. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. A prolonged in vitro drug release profile was observed. The release profiles of finasteride from PPC and PPCL microcapsules were found to occur with a burst release followed by a gradual release phase. Drug release rates were dependent upon the properties of the polymer in the microspheres, the higher hydrolytic activity of polymer provided faster release rate.     

Novel blend microspheres of poly(3‐hydroxybutyrate) and Pluronic F68/127 for controlled release of 6‐mercaptopurine

The objective of this article is to investigate the controlled release characteristics of 6‐mercaptopurine (6‐MP) loaded microspheres prepared from the blends of poly(3‐hydroxybutyrate) (PHB) and Pluronic F68/127 by the oil‐in‐water emulsion‐solvent evaporation technique. Formulations were prepared by taking different ratios of individual polymer components to achieve a maximum 79% encapsulation and extending the release time up to 24 h. Differential scanning calorimetry (DSC) suggested reduction in crystallanity of PHB after blending with Pluronic F127. The absence of chemical interactions between 6‐MP and the blend matrix was confirmed by Fourier transform infrared (FTIR) spectroscopy, while the size of microspheres measured by optical microscopy ranged between 30 and 47 μm. X‐ray diffraction (XRD) confirmed the crystalline nature of 6‐MP even after encapsulation and surface morphology of the microspheres was investigated by scanning electron microscopy (SEM). In vitro release of 6‐MP at 37°C in pH 7.4 phosphate buffer media indicated a dependence on the composition of Pluronic in the blend. The release data have been fitted to empirical equations to understand the release profile of 6‐MP. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40196.     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

Mixed‐interpenetrated polymeric networks based on sodium alginate (ALG) and poly(N‐isopropylacryl amide) (PNIPAAm) covalently cross‐linked with N,N'‐methylenebisacrylamide are studied for their biocompatibility, nontoxicity, and biodegradability aiming their application in drug delivery. The presence of drug‐polymeric matrix interactions and the distribution of the drug in the polymeric network for theophylline‐loaded ALG/PNIPAAm hydrogels are also investigated by spectroscopic and microscopic methods. The quantitative evaluation of theophylline loaded hydrogels performed by NIR‐CI technique shows a better drug entrapment and a higher homogeneity of the samples with increased alginate content. The thermal behavior of the hydrogels is significantly modified by theophylline presence. The application of the ALG/PNIPAAm hydrogels as carriers for sustained drug release formulations was assessed by the theophylline release tests performed both by in vitro and in vivo studies. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40733.     

Formation of microcapsules of medicines by the rapid expansion of a supercritical solution with a nonsolvent

The rapid expansion from a supercritical solution with a nonsolvent (RESS‐N) was applied to the formation of polymeric microcapsules containing medicines such as p‐acetamidophenol, acetylsalicylic acid, 1,3‐dimethylxanthine, flavone, and 3‐hydroxyflavone. A suspension of medicine in carbon dioxide (CO₂) containing a cosolvent and dissolved polymer was sprayed through a nozzle to atmospheric pressure. The pre‐expansion pressure was 10–25 MPa, and the temperature was 308–333 K. The polymers were poly(L ‐lactic acid) (molecular weight = 5000), poly(ethylene glycol) (PEG; PEG4000, molecular weight = 3000; PEG6000, molecular weight = 7500; and PEG20000, molecular weight = 20,000), poly(methyl methacrylate) (molecular weight = 15,000), ethyl cellulose (molecular weight = 5000), and PEG–poly(propylene glycol)–PEG triblock copolymer (molecular weight = 13,000). The solubilities of the polymers as coating materials and these medicines as core substance were very low in CO₂. However, the solubilities of these polymers in CO₂ significantly increased with the addition of low molecular weight alcohols as cosolvents. After RESS‐N, polymeric microcapsules were formed according to the precipitation of the polymer caused by a decrease in the solvent power of CO₂. This method offered three advantages: (1) enough of the coating polymers, which were insoluble in pure CO₂, dissolved; (2) the microparticles of the medicine were encapsulated without adhesion between the particles because a nonsolvent was used as a cosolvent and the cosolvent remaining in the mixture was removed by the gasification of CO₂; and (3) the polymer‐coating thickness was controlled with changes in the feed composition of the polymer for drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 742–752, 2003     

Poly(allyl glycidyl ether)‐block‐poly(ethylene oxide): A novel promising polymeric intermediate for the preparation of micellar drug delivery systems

Novel diblock copolymers designed for the preparation of micellar drug delivery systems, consisting of hydrophobic poly(allyl glycidyl ether) (PAGE) and hydrophilic poly(ethylene oxide) (PEO), were prepared, and their self‐assembly into micellar structures was studied. Copolymers differing in the length of the polymer blocks were purified and characterized. These amphiphilic copolymers with narrow molecular weight distributions were prepared through the anionic polymerization of allyl glycidyl ether with PEO monomethyl ether sodium salt as the macroinitiator. The PAGE–PEO copolymer readily formed small micelles with narrow size distributions via simple dissolution in water. The addition of pendant double bonds to the hydrophobic part of the chain was intended for further covalent modifications. Catalytic hydrogenation, the radical crosslinking of the micelle core, and the addition of thiol to double bonds of the copolymer were examples of such modifications that were proved to proceed with a quantitative yield for this copolymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 201–211, 2005