Porous, noncrosslinked polyelectrolyte-complex thin films (see figure), which will find applications in biomedicine, for example for drug or gene delivery, are achieved by using a simple, mild, and efficient method. Layer-by-layer assembly of polyanion and a blend of two polycations is followed by removal of the reductively degradable polycation template in the multilayered film in dithiothreitol solution.

Cholic acid functionalized star oligo/poly(DL-lactide)s with different molecular weights were synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. On the basis of the specific physicochemical properties of the star oligo/poly(DL-lactide)s, submicron sized drug-delivery systems were fabricated using a very convenient “ultrasonic dispersion method,” which did not involve toxic organic solvents. The drug-loaded microspheres had a regular spherical shape with a narrow size distribution. The effects of ultrasonic power and the molecular weight of polymers on the microsphere fabrication were investigated. The in vitro drug release was studied. The release profiles were fitted by the classical empirical exponential expression. The fitting result indicated that the drug release was controlled by combined degradation and diffusion mechanism. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007

A novel seven-arm star block copolymer poly(L-lactide-star block-N-isopropylacrylamide) (PLLA-sb-PNIPAAm), comprised of a hydrophobic poly(L-lactide) (PLLA) arm and an average of six hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms, was designed and synthesized. The amphiphilic PLLA-sb-PNIPAAm copolymer was capable of self-assembling into nano-sized micelle in water, which was confirmed by FT-IR, ¹H NMR and fluorescence spectroscopy. Transmission electron microscopy images showed that these nano-sized micelles were regularly spherical in shape. Micelle size determined by size analysis was around 100 nm in diameter. The micelles showed reversible dispersion/aggregation in response to temperature changes through an outer polymer shell of PNIPAAm at around 31°C, observed by optical absorbance measurements. The anticancer drug methotrexate (MTX) as model drug was loaded in the polymeric nano-sized micelles. In vitro release behavior of MTX was investigated, which showed a drastic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of a micellar shell structure. The reversible and sensitive thermoresponse of this micelle might provide opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

A novel biodegradable amphiphilic copolymer with hydrophobic poly(ε-caprolactone) branches containing cholic acid moiety and a hydrophilic poly(ethylene glycol) chain was synthesized. The copolymer was characterized by FTIR, ¹H NMR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), polarizing light microscopy (PLM), and wide-angle X-ray diffraction (WAXD) analysis. The amphiphilic copolymer could self-assemble into micelles in an aqueous solution. The critical micelle concentration of the amphiphilic copolymer was determined by fluorescence spectroscopy. A nanoparticle drug delivery system with a regularly spherical shape was prepared with high encapsulation efficiency. The in vitro drug release from the drug-loaded polymeric nanoparticles was investigated. Because of the branched structure of the hydrophobic part of the copolymer and the relatively fast degradation rate of the copolymer, an improved release behavior was observed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5256–5265, 2007

A series of star poly(ϵ-caprolactone)s (PCL) with dendritic cores, PAMAM-PCLs, were synthesized through the ring-opening polymerization of ϵ-caprolactone (CL) initiated by poly(amidoamine) dendrimer (PAMAM-OH). By controlling the feed ratio of the macroinitiator PAMAM-OH to the monomer CL, the star polymers with different branch lengths and properties can be obtained. The successful incorporation of PCL sequences onto the PAMAM-OH core was verified by FTIR, ¹H NMR, and combined size-exclusion chromatography and multiangle laser light scattering analysis. The in vitro degradation of PAMAM-PCLs was investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PAMAM-OH core. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity that depends on the polymer composition. Using the PAMAM-PCLs with different molecular weights, the 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. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006

Novel cholic acid functionalized star oligo/poly(DL-lactide)s with different molecular weights were synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. Compared with poly(DL-lactide), these star oligo/poly(DL-lactide)s show faster hydrolytic degradation rates, and the degradation mechanism changes from bulk erosion to surface erosion with decreasing molecular weight. Based on the specific physicochemical properties of the novel star oligo/poly(DL-lactide), the drug delivery system with submicron size was fabricated using a very convenient “ultrasonic dispersion method” which did not involve toxic organic solvents. The in vitro drug release was studied. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007

Novel ABA-type amphiphilic triblock copolymers composed of poly (ethylene glycol) (PEG) as hydrophilic segment and poly (2,2-dimethyltrimethylene carbonate) (PDTC) as hydrophobic segment were synthesized by ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) initiated by dihydroxyl PEG. The influence of introducing PEG block on crystalline behavior of PDTC segment was investigated by DSC. Polymeric micelles in aqueous medium were characterized by fluorescence spectroscopy and dynamic light scattering. The critical micelle concentration of these copolymers was in the range of 5.1–50.5 mg/L. Particle size was 80–280 nm. Core-shell–type nanoparticles were prepared by the dialysis technique. Zeta potential was measured by laser Doppler anemometry, and all nanoparticles had negative zeta potential. Transmission electron microscopy images demonstrated that these nanoparticles were spherical in shape. Anticancer drug 5-fluorouracil (5-Fu) as a model drug was loaded in the polymeric nanoparticles. X-ray powder diffraction demonstrated that 5-Fu was encapsulated into polymeric nanoparticles as molecular dispersion. In vitro cytotoxicity of nanoparticles was evaluated by MTT assay. In vitro release behavior of 5-Fu was investigated, and sustained drug release was achieved. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(L-lactide) (PLLA) sequences onto a water-soluble polymer poly-α,β-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. We established the feasibility of preparing these novel graft polymers by the ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The successful grafting of PLLA sequences onto the PHEA backbone was verified by combined size exclusion chromatography (SEC) and multiangle laser light scattering (MALLS) analysis. The chemical structures of graft polymers were characterized by FTIR and ¹H NMR. The critical micelle concentration (CMC) of the graft polymer was determined by fluorescence probe technique using pyrene. By controlling the feed ratio of the macroinitiator to the monomer, graft polymers with different branch lengths can be obtained. Using the 3-(4,5 dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, the graft copolymer has been proved to have low cytotoxicity. Based on the amphiphilicity of the graft copolymers, nanoparticular drug delivery systems were prepared by the direct dissolution method and the dialysis method. The anticancer drug Tegafur was encapsulated into polymeric nanoparticles, and in vitro drug release behavior was investigated. Transmission electron microscopy (TEM) images demonstrate that these nanoparticles are regularly spherical in shape. The particle size and distribution of the nanoparticles were measured. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Summary: Novel temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) nanoparticle-containing PNIPAAm hydrogels were prepared by radical polymerization. In comparison with conventional PNIPAAm hydrogels, the PNIPAAm gels thus prepared exhibit much faster response rates as the temperature is raised above the lower critical solution temperature. The improved properties are a result of the incorporation of PNIPAAm particles, which first shrink and then generate pores for water molecules to be quickly squeezed out of the bulky PNIPAAm gels.

Summary: The model drugs ibuprofen (IBU) and tegafur (T-Fu) were loaded into poly[N-isopropylacrylamide-co-(acryloyl β-cyclodextrin)] [P(NIPA-co-A-CD)] and PNIPA hydrogels by immersing dried gels in IBU or T-Fu alcohol solutions until they reached equilibrium. Drug release studies were carried out in water at 25 °C. In contrast to the release time of conventional PNIPA hydrogel, that of IBU from the β-CD incorporated hydrogel was significantly prolonged and the drug loading was also greatly increased, which may be the result of the formation of inclusion complexes between CD and ibuprofen. However, another hydrophilic drug, tegafur, did not display these properties because it could not form a complex with the CD groups.

Summary: A novel aliphatic polycarbonate based on ketal protected dihydroxyacetone was synthesized by ring-opening polymerization of cyclic carbonate monomer, 2,2-ethylenedioxypropane-1,3-diol carbonate (EOPDC), in bulk. Effects of polymerization conditions such as catalysts, catalyst concentration, reaction temperature and reaction time on the polymerization were investigated. The polycarbonate obtained was characterized by GPC, FTIR, ¹H NMR, ¹³C NMR and DSC. The study on in vitro degradation of PEOPDC shows that the degradation mainly results from surface erosion.

Summary: Poly(vinyl alcohol) (PVA) and polyamidoamine (PAMAM) dendrimers are water-soluble, biocompatible and biodegradable polymers, which have been widely applied in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of PVA and amine-terminated PAMAM dendrimer G6-NH₂ were prepared by cyclic freezing/thawing treatment of aqueous solutions containing PVA and G6-NH₂. The FT-IR analysis and elemental analysis indicated that PAMAM dendrimer G6-NH₂ was successfully introduced into the formed hydrogels, possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups in PVA and PAMAM dendrimer in the process of freezing-thawing cycle. Compared with physically cross-linked PVA hydrogel, PVA/G6-NH₂ hydrogels show higher swelling ratios and faster re-swelling rate due to the higher hydrophilicity of PAMAM dendrimer G6-NH₂. Higher contents of G6-NH₂ in PVA/G6-NH₂ hydrogels resulted in higher swelling ratios and faster re-swelling rates. With increasing freezing/thawing cyclic times, the swelling ratios and re-swelling rates of PVA/G6-NH₂ hydrogels decreased, which is similar to that of physically cross-linked PVA hydrogel. Combining the special host property of polyamidoamine dendrimer, these novel physically cross-linked hydrogels are expected to have potential use in drug delivery, including improving drug-loading amounts in hydrogels and prolonging drug release time.

Summary: Novel temperature-sensitive poly(N-isopropylacrylamide)/amine-terminated polyamidoamine dendrimer G6-NH₂ hydrogels with fast responsive properties were synthesized by forming semi-interpenetrating polymeric networks. In contrast to the conventional PNIPA hydrogel, these new gels showed rapid shrinking rate at the temperature above lower critical solution temperature (LCST), and exhibited higher equilibrium swelling ratio at room temperature. All these properties might be attributed to the incorporation of polyamidoamine dendrimer G6-NH₂, which forms water-releasing channels and increases the hydrophilicity of PNIPA network. The novel hydrogels have potential applications in drug and gene delivery.

Summary: Novel temperature sensitive poly(N-isopropylacrylamide-co-acryloyl beta-cyclodextrin) (P(NIPA-co-A-CD)) hydrogels with fast shrinking rates were prepared by radical polymerization of NIPA, A-CD and crosslinker in a mixture of water/1,4-dioxane as solvent. Because the mixed solvent was a poor solvent for the copolymers, phase separation occurred during the polymerization, which resulted in a heterogeneous, porous structure of the hydrogels. In contrast to the normal PNIPA hydrogel and the homo P(NIPA-co-A-CD) gel prepared in water, the P(NIPA-co-A-CD) hydrogels synthesized in water/1,4-dioxane as solvent exhibited higher swelling ratios at the temperature below the lower critical solution temperature (LCST) and shrunk rapidly to equilibrium within shorter time when the temperature was increased above LCST. Increasing the acryloyl beta-cyclodextrin content in the gels led to a slight decrease of the swelling ratio at lower temperature and had no marked influence on the shrinking kinetics. The gels prepared in water/1,4-dioxane, at different v/v ratios of 1.0/0.2, 0.8/0.4 and 0.6/0.6, showed similar properties.

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(2,2-dimethyltrimethylene carbonate) sequences onto a water-soluble polymer poly-α,β-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. We established the feasibility of preparing these novel graft polymers by the ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The successful grafting of poly(2,2-dimethyltrimethylene carbonate) sequences onto the PHEA backbone was verified by combined size exclusion chromatography and multi-angle laser light scattering analysis. The chemical structures of graft polymers were characterized by Fourier transform infrared and ¹H NMR. By controlling the feed ratio of the monomer to the macroinitiator, graft polymers with different hydrophilicities can be easily obtained.

In this article, the synthesis and characterization of novel hydrogel systems designed for colon-targeting drug delivery are reported. The gels were composed of konjac glucomannan, copolymerized with acrylic acid, and crosslinked by the aromatic azo agent bis(methacryloylamino)-azobenzene. The influence of various parameters on the dynamic and equilibrium swelling ratios (SRs) of the hydrogels was investigated. It is shown that the SR was inversely proportional to the grafting degree of acrylic acid and the content of bis(methacryloylamino)-azobenzene. The dependence of SR on the pH indicates that obtained hydrogels are potential for drug delivery to colon. It was possible to modulate the degree of swelling and the pH sensitivity of the gels by changing crosslinking density of the polymer. The main chain of hydrogels can be degraded by β-glycosidase which is abundant in colon. They can be in vitro degraded for 73% in a month by Cereflo® and 86% in 20 days by Mannaway25L. We have also prepared the hydrogels that loaded with bovine serum albumin about 1.5%, 3%, 9%, and 20% by weight. In vitro release of model drug bovine serum albumin was studied in the presence of Mannaway25L or Fungamyl®800L in pH 7.4 phosphate buffer at 37 °C. The drug release can be controlled by the biodegradation of the hydrogels. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4370–4378, 2004

A series of novel biodegradable random copolymers of 5-benzyloxy-1,3-dioxan-2-one (5-benzyloxy-trimethylene carbonate, BTMC) and glycolide were synthesized by ring-opening polymerization. The copolymers were characterized by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The incorporation of BTMC units into the copolymer chains results in good solubility of the polymers in common solvents. The in vitro degradation rate can be tailored by adjusting the composition of the copolymers.

Macroporous temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) hydrogels were prepared by a novel phase-separation technique to improve the response properties. In comparison with a conventional PNIPA hydrogel prepared in water, these macroporous hydrogels, prepared by polymerization in aqueous sucrose solutions, have higher swelling ratios at temperatures below the lower critical solution temperature and exhibit much faster response rates to temperature changes.

Novel linear poly(NIPA-co-CL) copolymers have been synthesized by radical copolymerization of N-isopropylacrylamide (NIPA) and 2-methylene-1,3-dioxepane (MDO). The structure of copolymers was confirmed by ¹H NMR and IR spectroscopy. Cross-linked poly(NIPA-co-CL) hydrogels have also been prepared in toluene using N,N′-methylenebisacrylamide as cross-linking agent. The hydrogels thus obtained exhibit good temperature response and are biodegradable in the presence of proteinase K.

A series of temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) hydrogels with large pore size and fast response were prepared by carrying out polymerizations in aqueous sodium chloride solutions with different concentrations. In comparison with conventional PNIPA hydrogels, the PNIPA gels thus prepared have remarkably larger swelling ratios below their lower critical solution temperature (LCST), and exhibit much faster response rates as the temperature is raised above their LCST. The improved properties are due to the presence of inorganic salt, NaCl, which leads the phase separation and formation of a heterogeneous porous structure during the polymerizations. The study on the drug release properties shows the macroporous hydrogels exhibit modulated release in response to temperature. The model protein, bovine serum albumin (BSA), can be released completely from the porous hydrogels at the temperature lower than the LCST because the pore size of the hydrogels is larger than the protein molecules. However, the release of BSA from the gels almost stops after a “burst” release in the initial stage at the temperature higher than the LCST because the pores are closed at the high temperature. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 96–103, 2003

Two, functional, cyclic carbonate monomers, 5-methyl-5-methoxycarbonyl-1,3-dioxan-2-one and 5-methyl-5-ethoxy carbonyl-1,3-dioxan-2-one, were synthesized starting from 2,2-bis(hydroxymethyl) propionic acid. The ring-opening polymerization of the cyclic carbonate monomers in bulk with stannous 2-ethylhexanoate as a catalyst under different conditions was examined. The results showed that the yield and molecular weight of polycarbonates were significantly influenced by the reaction conditions. The polycarbonates obtained were characterized by IR, ¹H NMR, and differential scanning calorimetry. Their molecular weight was measured by gel permeation chromatography. The in vitro biodegradation and controlled drug-release properties of the polycarbonates were also investigated. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 4001–4006, 2003