Synthesis of an esterase‐sensitive degradable polyester as facile drug carrier for cancer therapy

Polyethylene glycol (PEG) is widely used as a carrier to improve the pharmaceutical properties of drugs with low molecular weight. However, PEG has few functional groups (usually two) for drug conjugation and the resulting low drug content (1–2%) has hampered its clinical applications. For this study, we synthesized biodegradable poly(ethylene glycol‐co‐anhydride). This polyester‐based polymer possesses multiple carboxylic acid groups that can be used as facile drug carriers. Two anticancer drugs, camptothecin (CPT) and doxorubicin (DOX) were loaded into the carrier and their releasing properties and in vitro anticancer activities were studied. The polymer–drug conjugates exhibited esterase‐promoted degradation and drug release. Their cytotoxicity against the human ovarian cancer cell line SKOV‐3 was comparable to unconjugated drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 507–515     

Synthesis of spherical and hemispherical sugar‐containing poly(ornithine) dendrimers

A novel sugar‐containing poly(ornithine) dendrimer is synthesized for possible antigen delivery and related applications. The dendrimer contains an ornithine dendron as interior scaffolding and oligosaccharides on the periphery, which provide an attachment site for a peptide antigen. Maltose or lactose is bound to both hemispherical and spherical poly(ornithine) dendrimer generation 3 (G3) by reductive amination between its reducing end and the peripheral amino group of the dendrimer using a borane‐pyridine complex in a buffer solution at 50 °C. The degree of substitution of sugar is changed by varying the molar ratio of sugar to dendrimer. When the surface of spherical poly(ornithine) dendrimer G3 is modified by binding β‐alanine to the 16 amino groups, highly substituted maltose‐ or lactose‐β‐alanine‐poly(ornithine) dendrimer G3 is obtained in high yield after 7 days of reaction. The structures of these sugar‐containing dendrimers are characterized by NMR and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry analyses. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1400–1414, 2004     

Synthesis and characterization of biodegradable amphiphilic ABC Y‐shaped miktoarm terpolymer by click chemistry for drug delivery

Biodegradable amphiphilic ABC Y‐shaped triblock copolymer (MPBC) containing PEG, PBLA, and PCL segments was synthesized via the combination of enzymatic ring‐opening polymerization (ROP) of epsilon‐caprolactone, ROP of BLA‐N‐carboxyanhydride and click chemistry, where PEG, PBLA, and PCL are poly(ethylene glycol), poly(benzyl‐l ‐aspartate), and polycaprolactone, respectively. Propynylamine was employed as ROP initiator for the preparation of alkynyl‐terminated PBLA and methyloxy‐PEG with hydroxyl and azide groups at the chain‐end was used as enzymatic ROP initiator for synthesis of monoazido‐midfunctionalized block copolymer mPEG‐b‐PCL. The subsequent click reaction led to the formation of Y‐shaped asymmetric heteroarm terpolymer MPBC. The polymer structures were characterized by different analyses. The MPBC terpolymer self‐assembled into micelles and physically encapsulated drug doxorubicin (DOX) to form DOX‐loaded micelles, which showed good stability and slow drug release. In vitro cytotoxicity study indicated that the MPBC micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3346–3355     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39     

Synthesis of dicarboxylate oligosaccharide multilayer terminal functionality upon poly(lysine) dendrimer scaffolding

A reactive three‐layered dendrimer containing carboxyl groups was synthesized by the coupling of dicarboxylic acid and a highly reactive, two‐layered glycopeptide dendrimer. Lactose, maltose, or maltotriose was reacted with the poly(lysine) dendrimer in its third and fourth generations by reductive amination and afforded two‐layered glycolysine dendrimers. The reaction was conducted in a borate buffer (pH 9.0). ¹H NMR, ¹³C NMR, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry analyses were applied for the determination of the structures of the products. When an excess amount of the oligosaccharide and a long reaction time were used, the degree of substitution increased to 1.5–2.0 against an amino group. For the preparation of highly reactive, multilayered dendrimers for an antigen carrier, C6 hydroxy groups of the oligosaccharides were selectively esterified by adipic acid and suberic acid to give 6‐O‐adipoyl oligosaccharide–poly(lysine) dendrimers and 6‐O‐suberoyl oligosaccharide–poly(lysine) dendrimers. The reactivity of these multilayered dendrimers was examined by a model reaction with phenylalanine ethyl ester. The dendrimer showed high reactivity, providing phenylalanine ethyl ester–dicarboxylate oligosaccharide–poly(lysine) dendrimers with a considerably high proportion of phenylalanine residues. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3622–3633, 2002     

Gelation characteristics and applications of poly(ethylene glycol) end capped with hydrophobic biodegradable dipeptides

Poly(ethylene glycol) (PEG) end capped with biodegradable hydrophobic dipeptides shows versatile gelation behavior in a wide range of aqueous and organic solvents. This gelation characteristic is attributed to the aggregation of polymer chains induced by dipeptide end groups. Both PEG molecular weight and molecular structure of end groups control this aggregation by striking a balance between two opposing molecular interactions: solubility of the PEG segment which tends to dissolve the polymer while hydrophobic and intermolecular noncovalent interactions between the end groups induce aggregation. Morphologically, this aggregated structure forms interpenetrating nano sheets with characteristic microstructural features. These gels are biodegradable and possess physicomechanical characteristics suitable for biomedical applications. Furthermore, proteins and hydrophobic model drugs can be encapsulated within the gels from aqueous and organic solvents, respectively, and can be released in a controlled fashion which indicates the applicability of the gels as drug delivery vehicles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1917–1928     

Approach to peptide decorated micelles via RAFT polymerization

Pyridyldisulfide (PDS) functionalized telechelic polymers of oligo(ethyleneglycol) acrylate (PEG‐A) and their amphiphilic triblock copolymers with styrene (St) were synthesized directly by reversible addition‐fragmentation chain transfer (RAFT) polymerization using a new bifunctional RAFT agent, S,S‐bis[α,α′‐dimethyl‐α″‐(2‐pyridyl disulfide) ethyl acetate] trithiocarbonate (BDPET). The homopolymerization of PEG‐A was found to be well controlled using BDPET (PDI < 1.2). The ABA triblock copolymers poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) with narrow molecular weight distribution (PDI < 1.25) were synthesized using poly(PEG‐A) as a macro‐RAFT agent. UV‐vis spectroscopic analysis revealed that 85 mol % of poly(PEG‐A) and 78 mol % of poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) retained PDS end group functionality. Micelles were observed to form from poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A). The presence of PDS groups within the micelle corona was evidenced by UV‐vis spectroscopy and fluorescence spectroscopy. The PDS groups within the corona were then used to functionalize the micelles with a thiol group bearing model peptide, reduced glutathione, and a thiol modified fluorophore, rhodamine B, under mild reaction conditions. UV‐vis and fluorescence spectrocopies revealed that approximately 80% PDS groups from the amphiphilic copolymer were tethered within the micelle coronas and accessible to glutathione and fluorophore attachment. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 899–912, 2009     

Chemical modification of poly(methylphenylsiloxane)

Poly(methylphenylsiloxane) (PMPS) with a narrow molecular weight distribution (MWD) was prepared by anionic polymerization, and ring‐functionalized using procedures optimized to minimize chain degradation. The products were characterized by NMR and IR spectroscopy, and the MWD of the polymers was analyzed by size exclusion chromatography, to monitor polymer degradation and crosslinking during the functionalization reactions. Electrophilic substitution was used to introduce nitro and bromo groups on the phenyl ring of the polymer. Nitration with fuming nitric acid yielded up to 8 mole % substitution with some chain degradation. Bromination was achieved with bromine in the presence of either pyridine or triethylamine. A substitution level of up to 14 mole % and a small increase in the polydispersity index (M_w/M_n) were obtained with triethylamine. Hydroxyethyl functionalities were obtained by lithiation of the brominated PMPS via metal‐halogen exchange, and reaction with ethylene oxide. A polymer with 3 mole % hydroxyethyl functionalities was obtained with moderate chain degradation. A substitution level of 6 mole % could be achieved under different conditions, but with more extensive chain degradation. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 653–664, 1999     

Core‐stabilized polymeric micelle as potential drug carrier: increased solubilization of taxol

Poly(ethylene glycol‐b‐lactide) possessing a methoxy group at the poly(ethylene glycol) (PEG) chain end and a polymerizable methacryloyl group at the poly(lactic acid) (PLA) chain end (MeO–PEG/PLA–methacryloyl) was prepared by an anionic ring‐opening polymerization of ethylene oxide and DL ‐lactide in tandem manner initiated with a potassium 2‐methoxyethanolate, followed by end‐capping with an excess of methacrylic anhydride. The molecular weight of the obtained polymer was controlled by the initial monomer/initiator ratio, which was confirmed by the combination of gel permeation chromatography and nuclear magnetic resonance analyses. The functionality of the methacryloyl–PLA end was almost quantitative. The MeO–PEG/PLA–methacryloyl (38/35; these numbers in parentheses denote the molecular weights of PEG and PLA segments divided by 100, respectively) formed a core–shell type spherical micelle in aqueous media obtained by a dialysis technique, the cumulant diameter of which was ca. 30 nm with very low polydispersity factor. The methacryloyl group adjacent to the PLA was polymerized in the PLA core of the micelle. The polymerization proceeded thermally with radical initiator and photochemically with photo‐initiator to produce core‐polymerized nanoparticles, which was found by spectroscopic and light‐scattering techniques. Taxol‐incorporated micelles were prepared to entrap Taxol into MeO–PEG/PLA–methyacryloyl block copolymer micelles by the oil/water emulsion method. Copyright © 1999 John Wiley & Sons, Ltd.     

Easily grafted polyurethanes with reactive main chain functional groups. Synthesis,characterization, and antithrombogenicity of poly(ethylene glycol)-grafted poly(urethanes)

A novel synthesis of poly(ethylene glycol) (PEG)-grafted poly(urethanes) (PURs) is described based on a precursor PUR containing free amino groups in the main chain. Three different poly(urethane) backbones were prepared: a homopoly(urethane) comprised of N-Bocdiethanolamine (BDA) and 4,4′-methylenebis(phenyl isocyanate) (MDI), a copoly(urethane) (COPUR) consisting of BDA, N-benzyldiethanolamine and MDI, and a poly(urethane urea) (PUU) that was prepared from BDA, MDI, and ethylenediamine as the chain extender. The M_n of these poly(urethanes) ranged from 32,000 to 72,000 g/mol. PEG (750, 1,900, and 5,000 g/mol) was grafted onto the boc-deprotected poly(urethanes) via the chloroformate. Films of the polymers were spin cast from dilute solutions, annealed, and the surfaces analyzed by goniometry. Water contact angle data indicates increasing PEG surface coverage of the poly(urethanes) with increasing PEG molecular weight. Reorientation of the polymer films is evidenced by contact angle hysteresis. Polymer thrombogenicity, which was studied using blood perfusion experiments, shows that COPUR-g-PEG5000 and PUU-g-PEG5000 exhibit very little platelet adhesion. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3441–3448, 1999     

Thermosensitive permeation from side‐chain crystalline ionomers

Poly(stearyl methacrylate‐co‐methacrylic acid) (SMA) and its sodium ionomer (SMI) were synthesized and the permeability of the model drug through the SMA and SMI films was measured. The side‐chain crystalline structure for the dried and hydrated SMA, SMI was investigated using DSC and WAXS. The side‐chain crystalline structure of the hydrated SMI was much more stable than that of the hydrated SMA at room temperature. The temperature‐sensitive phase transition of the side‐chain crystalline structure for the hydrated SMI was also studied by the temperature variable WAXS experiment. The temperature‐sensitive permeation of the hydrophilic model drug through SMI was observed around 20 °C, whereas the drug permeation through SMA was almost constant within the temperature range studied. The change of drug permeability through the SMA and SMI films with temperature seems to be associated with the side‐chain crystalline structure of the polymer. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 823–830, 2000     

Y‐shaped poly(ethylene glycol) and poly(trimethylene carbonate) amphiphilic copolymer: Synthesis and for drug delivery

New Y‐shaped (AB₂‐type) amphiphilic copolymers of poly(ethylene glycol) (PEG) with poly(trimethylene carbonate) (PTMC), PEG‐b‐(PTMC)₂, were successfully synthesized by the ring‐opening polymerization (ROP) of TMC with bishydroxy‐modified monomethoxy‐PEG (mPEG). First, a bishydroxy functional ROP initiator was synthesized by esterification of acryloyl bromide with mPEG, followed by Michael addition using excess diethanolamine. A series of Y‐shaped amphiphilic PEG‐(PTMC)₂ block copolymers were obtained via ROP of TMC using this PEG with bishydroxyl end groups as macroinitiator and ZnEt₂ as catalyst. The amphiphilic block copolymers with different compositions were characterized by gel permeation chromatography (GPC) and ¹H NMR, and their molecular weight was measured by GPC. The results showed that the molecular weight of Y‐shaped copolymers increased with the increase of the molar ratio of TMC to mPEG‐(OH)₂ initiator in feed while the PEG chain length was kept constant. The Y‐shaped copolymer mPEG‐(PTMC)₂ could self‐assemble into micelles in aqueous medium and the critical micelle concentration values of the micelles decrease with increase in hydrophobic PTMC block length of mPEG‐(PTMC)₂. The in vitro cytotoxicity and controlled drug release properties of the Y‐shaped amphiphilic block copolymers were also investigated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8131–8140, 2008     

Synthesis and characterization of a multiarm poly(acrylic acid) star polymer for application in sustained delivery of cisplatin and a nitric oxide prodrug

Functionalized polymeric nanocarriers have been recognized as drug delivery platforms for delivering therapeutic concentrations of chemotherapies. Of this category, star‐shaped multiarm polymers are emerging candidates for targeted delivery of anticancer drugs, due to their compact structure, narrow size distribution, large surface area, and high water solubility. In this study, we synthesized a multiarm poly(acrylic acid) star polymer via macromolecular design via the interchange (MADIX)/reversible addition fragmentation chain transfer (MADIX/RAFT) polymerization and characterized it using nuclear magnetic resonance (NMR) and size exclusion chromatography. The poly(acrylic acid) star polymer demonstrated excellent water solubility and extremely low viscosity, making it highly suited for targeted drug delivery. Subsequently, we selected a hydrophilic drug, cisplatin, and a hydrophobic nitric oxide (NO)‐donating prodrug, O²‐(2,4‐dinitrophenyl) 1‐[4‐(2‐hydroxy)ethyl]‐3‐methylpiperazin‐1‐yl]diazen‐1‐ium‐1,2‐diolate, as two model compounds to evaluate the feasibility of using poly(acrylic acid) star polymers for the delivery of chemotherapeutics. After synthesizing and characterizing two poly(acrylic acid) star polymer‐based nanoconjugates, poly(acrylic acid)–cisplatin (acid–Pt) and poly(acrylic acid–NO (acid–NO) prodrug, the in vitro drug release kinetics of both the acid–Pt and the acid–NO were determined at physiological conditions. In summary, we have designed and evaluated a polymeric nanocarrier for sustained‐delivery of chemotherapies, either as a single treatment or a combination therapy regimen. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Structural analysis of poly(amidoamine) dendrimer immobilized in crosslinked poly(ethylene glycol)

Polymeric membranes comprised of poly(amidoamine) (PAMAM) dendrimer immobilized in a poly(ethylene glycol) (PEG) network exhibit an excellent CO₂ separation selectivity over H₂. The CO₂ permeability increases with PAMAM dendrimer concentration in the polymeric membrane and becomes 500 times greater than H₂ permeability when the dendrimer content was 50 wt % at ambient conditions (5 kPa of CO₂ partial pressure). However, the detailed morphology of the membrane has not been discussed. The immiscibility of PAMAM dendrimer and PEG matrix results in phase separation, which takes place in a couple of microns scale. Especially, laser scanning confocal microscope captures a 3D morphology of the polymeric blend. The obtained 3D reconstructions demonstrate a bicontinuous structure of PAMAM dendrimer‐rich and PEG‐rich phases, which indicates the presence of PAMAM dendrimer channel penetrating the polymeric membrane, and CO₂ will preferentially pass through the dendrimer channel. In addition, Fourier transform of the 3D reconstructions indicates the presence of a periodic structure. An average size of the dendrimer domain calculated is 2–4 μm in proportion to PAMAM dendrimer concentration. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Synthesis of self‐assembled sphingolipid conjugates and their morphology effect on anticancer therapeutic potency

The shape of self‐assembling polymer–drug conjugates, influencing the cellular uptake, is one of the important factors to be considered for effective drug delivery. In this study, we described synthesis of polymeric drug conjugates of different morphologies with phytosphingosine (PHS) as a hydrophobic model drug and poly(amino acid) as a hydrophilic host polymer. By varying the amount of PHS grafted to poly(amino acid), PHS–poly(amino acid) conjugates exhibited morphological transition from spherical to worm‐like micellar aggregates in the aqueous media. We investigated the physicochemical properties of self‐assembled structures in terms of hydrodynamic size, surface charge, and critical aggregation concentration. The anticancer therapeutic potency of these self‐assembled structures was also discussed in terms of cellular uptake and cytotoxicity of prodrug micelles as a function of dose and time by in vitro cell study. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of end‐functionalized AB copolymers. II. Synthesis and characterization of carboxyl‐terminated poly(ethylene glycol)–poly(amino acid) block copolymers

AB block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(amino acid) with a carboxyl group at the end of PEG were synthesized with α‐carboxylic sodium‐ω‐amino‐PEG as a macroinitiator for the ring‐opening polymerization of N‐carboxy anhydride. Characterizations by ¹H NMR, IR, and gel permeation chromatography were carried out to confirm that the diblock copolymers were formed. In aqueous media this copolymer formed self‐associated polymer micelles that have a carboxyl group on the surface. The carboxyl groups located at the outer shell of the polymeric micelle were expected to combine with ligands to target specific cell populations. The diameter of the polymer micelles was in the range of 30–80 nm. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3527–3536, 2004     

Synthesis and characterization of hyperbranched aromatic poly(ether imide)s with terminal amino groups

We synthesized an AB₂‐type monomer, 4‐{4‐[di(4‐aminophenyl)methyl]phenoxy}phthalic acid, which contained one phthalic acid group and two aminophenyl functionalities. The direct self‐polycondensation of the AB₂‐type monomer in the presence of triphenylphosphite as an activator afforded a hyperbranched poly(ether imide) with a large number of terminal amino groups. This polymer was characterized with ¹H NMR and IR spectroscopy. The degree of branching of the hyperbranched poly(ether imide) was approximately 56%, as determined by a combination of model compound studies and an analysis of ¹H NMR spectroscopy integration data. The terminal amino groups underwent functionalization readily. The solubility and thermal properties of the resulting polymers depended on the nature of the chain end groups. In addition, the hyperbranched poly(ether imide) was grafted with polyhedral oligomeric silsesquioxane (POSS). Transmission electron microscopy analysis revealed that the grafted POSS molecules aggregated to form a nanocomposite material. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3726–3735, 2003     

Well‐defined drug‐conjugated biodegradable nanoparticles by azide–alkyne click crosslinking in miniemulsion

A new type of biodegradable polymer–drug nanoconjugate was fabricated via the combination of oil‐in‐water miniemulsion and Huisgen azide–alkyne click chemistry. Diazide‐functionalized paclitaxel (PTXL) were prepared through functional group transformation on the C‐2′ and C‐7 positions of PTXL and served as both drug carrier and crosslinker. Acetylene‐functionalized polylactide (PLA) was used as the base polymer. Oil‐in‐water miniemulsion technique was used to create nanodroplets with diameters of round 50 nm, which were used as nanoreactors to control the size and morphology of the drug conjugates. Using sodium ascorbate/CuSO₄·5H₂O as catalysts, click reaction was performed within the nanodroplets between the azide functionalities of the PTXL‐based crosslinker and the pendant acetylene groups of the functional PLA. High extent of reaction was confirmed by FTIR analysis and the resulting drug‐conjugated nanoparticles were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy measurements. These NPs exhibited considerable degradation in proteinase K solution within 1 week. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Postfunctionalization of polyoxanorbornene via sequential Michael addition and radical thiol‐ene click reactions

We demonstrated the successful postfunctionalization of poly(oxanorbornene imide) (PONB) with two types of double bonds using sequential orthogonal reactions, nucleophilic thiol‐ene coupling via Michael addition and radical thiol‐ene click reactions. First, the synthesis of PONB with side chain acrylate groups is carried out via ring‐opening metathesis polymerization and nitroxide radical coupling reaction, respectively. Subsequently, the resulting polymer having two different orthogonal functionalities, main chain vinyl and side chain acrylate, is selectively modified via two sequential thiol‐ene click reactions, nucleophilic thiol‐ene coupling via Michael addition and photoinduced radical thiol‐ene. The orthogonal reactivity of two diverse double bonds, vinyl and acrylate functionalities, for the abovementioned consecutive thiol‐ene click reactions was first demonstrated on the model compound. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

UV-curable poly(ethylene glycol)–based polyurethane acrylate hydrogel

Poly(ethylene glycol) (PEG) with molecular weight (M_n) of 1000, 2000, 3000, and 4000 g/mol, four types of diisocyanate [hexamethylene diisocyanate (HDI), 4,4′-dicyclohexylmethane diisocyanate (H₁₂MDI), isophorone diisocyanate (IPDI), and toluene diisocyanate (TDI)], two types of comonomers [acrylamide (AAm) and acrylic acid (AAc)] that comprised up to 60% of the total solid were used to prepare UV-curable PEG–based polyurethane (PU) acrylate hydrogel. The gels were evaluated in terms of mechanical properties, water content as a function of immersion time and pH, and X-ray diffraction profiles of dry and swollen films. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2703–2709, 1999