A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poly (ethylene glycol)

A new mucoadhesive polymer was prepared by template polymerization of acrylic acid in the presence of poly(ethylene glycol) (PEG). FTIR results indicated that a polymer complex was formed between poly(acrylic acid) (PAA) and PEG through hydrogen bonding. The hydrogen bonding in the PAA/PEG polymer complex was stronger than that in the PAA/PEG blend, and became stronger as the molecular weight of PEG increased. Glass transition temperatures (T_g) of PAA in the PAA/PEG polymer complexes was shifted to a lower temperature than that of PAA in the PAA/PEG blend. However, they tended to become higher as the molecular weight of PEG increased. The dissolution rate of the PAA/PEG polymer complex was much slower than the PAA/PEG blend, and was dependent on pH and molecular weight of the PEG. The mucoadhesive force of the PAA/PEG polymer complexes was stronger than for the PAA/PEG blend or a commercial product, Carbopol 971P NF. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 2749–2754, 1999     

A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poloxamer

A new mucoadhesive polymer was prepared by template polymerization of acrylic acid using poloxamer as a template polymer. FTIR results showed that the interpolymer complex was formed by hydrogen bonding between the carboxyl group of poly(acrylic acid) (PAA) and the ether group of poloxamer. The extent of hydrogen bonding in the PAA/poloxamer interpolymer complex increased as the ratio of PAA/poloxamer decreased. The T_g of PAA/poloxamer interpolymer complexes was matched well with the T_g calculated by Gordon‐Taylor's equation than that of their blends. This result suggests that the PAA and poloxamer in the interpolymer complexes are more compatible than their blends. The dissolution rate of PAA/poloxamer interpolymer complexes was much slower than that of their blends, and was dependent on the pH of the medium and the ratio of PAA/poloxamer. The adhesive bond strength of PAA/poloxamer interpolymer complexes to a plastic (polypropylene) plate was greater than their blends or a commercial product, Carbopol 971P NF. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1525–1530, 2001     

Novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of silk sericin

A novel mucoadhesive polymer was prepared by template polymerization of acrylic acid in the presence of sericin for a transmucosal drug‐delivery (TMD) system. FTIR results indicated that a polymer complex was formed between poly(acrylic acid) (PAA) and sericin through hydrogen bonding. The glass transition temperatures (T_g's) of sericin and PAA in the PAA/sericin polymer complex were inner‐shifted compared with the T_g's of sericin and PAA themselves. This may be due to the increased miscibility of PAA with sericin through hydrogen bonding. The dissolution rate of the PAA/sericin interpolymer complex was dependent on the pH. The mucoadhesive force of the PAA/sericin polymer complex was similar to that of a commercial product, Carbopol 971P NF. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 274–280, 2001     

A mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poly(vinyl alcohol) for mucosal drug delivery

The interpolymer complexes composed of PVA and PAA were prepared by template polymerization of acrylic acid in the presence of PVA with different molecular weights and degrees of saponification. The carbonyl absorption band of the PAA in the PAA/PVA interpolymer complexes was shifted to a lower wavenumber due to H‐bonding between the carboxyl group of PAA and the hydroxyl group of PVA. The swelling ratio and the degree of dissolution of the PVA/PAA interpolymer complexes were dependent on the pH of the medium, the molecular weight, and the degree of saponification of the PVA. The release rate of a model drug, lidocaine, from the complexes decreased with increasing degree of saponification of the PVA due to the lower swelling degree of the complex. The adhesive force of the PVA/PAA interpolymer complexes with a plastic plate (poly propylene) was stronger than that of the commercial Carbopol 971P. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 327–331, 2004     

Characteristics of poly(vinyl pyrrolidone)/poly(acrylic acid) interpolymer complex prepared by template polymerization of acrylic acid: Effect of reaction solvent and molecular weight of template

Poly(vinyl pyrrolidone) (PVP)/poly(acrylic acid) (PAA) interpolymer complexes were prepared, in ethanol or dimethylformamide (DMF), by template polymerization of acrylic acid in the presence of PVP (MW: 42.5 or 1100 K) used as the template. FTIR analysis showed that the complexes were formed through hydrogen bonding between the carboxyl groups of the PAA and the carbonyl groups of the PVP. The glass‐transition temperature (T_g) of the complex, prepared in ethanol, was higher than that of the component polymers, whereas the T_g of the complex, prepared in DMF, was located between that of the component polymers. The dissolution rate of the complex was affected by the molecular weight of the PVP and the reaction solvent. The release rate of ketoprofen from the complexes showed a pH dependency, and was slower at a lower pH. The ketoprofen release rate from the complex was controlled mainly by the dissolution rate of the complex above the pK_a of PAA (4.75) and by the diffusion rate below the pK_a. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2390–2394, 2004     

Characterization and emulsifying properties of block copolymers prepared from lactic acid and poly(ethylene glycol)

Block copolymers were prepared by the direct polycondensation of an aqueous lactic acid solution on monomethoxy or dihydroxyl poly(ethylene glycol) (PEG) in the absence of a catalyst. The resulting poly(lactic acid) (PLA)–PEG diblock and PLA–PEG–PLA triblock copolymers were characterized by various analytical techniques, including matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF MS), gel permeation chromatography, and ¹H‐NMR. The molecular structure between PLA–PEG and PLA–PEG–PLA could be distinguished after the calculation of the repeat unit masses and end‐group masses through the MALDI‐TOF MS spectra. Interestingly, both copolymers could serve as a hydrophilic emulsifier to stabilize the squalene/water interfaces and yield narrowly distributed oil‐in‐water nanoparticles. In contrast, the prepolymer PEG failed to stabilize the squalene/water interface under the same homogenization conditions. These features are of great interest for applications as bioactive agent delivery, especially for candidate vaccine antigens and lipophilic anticancer drugs. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Kinetics and reaction mechanism of template polymerization investigated by conductimetric measurements Part 4. Radical polymerization of acrylic acid in the presence of poly(vinyl alcohol): characterization of resulting polymer blends

The radical polymerization of acrylic acid in the presence of poly(vinyl alcohol) as a template in aqueous solution has been studied using conductimetry, which shows template influences on the reaction rate. A comparison is made between data obtained by differential scanning calorimetry and infrared spectroscopy for poly(acrylic acid)–poly(vinyl alcohol) blends prepared either by template polymerization or by casting of the preformed polymers. Evidence for more significant interpolymer interactions in blends prepared by template polymerization than in those obtained by simple mixing is given. © 2001 Society of Chemical Industry     

Physicochemical characterization of poly(ethylene glycol) plasticized poly(methyl vinyl ether‐co‐maleic acid) films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether‐co‐maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Kinetics and reaction mechanism of template polymerization investigated by conductimetric measurements. Part 3. Radical polymerization of acrylic acid in the presence of poly(N‐vinylpyrrolidone)

Conductimetry was used for monitoring the radical polymerization of a weak electrolyte (acrylic acid) in aqueous solution and for determination of the kinetic parameters of the reaction (reaction order with respect to monomer, activation energy). The results obtained were consistent with those determined by other techniques (such as dilatometry) or expected from theory. Dilatometric and conductimetric measurements were also used to study the template polymerization of acrylic acid onto poly(N‐vinylpyrrolidone). Results indicate that the reaction proceeds according to a pick‐up mechanism. Complexes between poly(acrylic acid) and poly(N‐vinylpyrrolidone) were always isolated in equimolar composition of the two polymers, regardless of the polymerization mixture composition. Spectroscopic evidence of the existence of strong interaction and intimate mixing of the two polymers in the complexes was found. An influence of the template molecular weight on the chain length of the forming poly(acrylic acid) was detected by means of viscometry. © 2000 Society of Chemical Industry     

Enzyme-catalyzed ring-opening polymerization of cyclic esters in the presence of poly(ethylene glycol)

Low-molecular-weight polyesters were obtained by the ring-opening homopolymerization and copolymerization reaction of ϵ-caprolactone, rac- or L -lactide, and glycolide in the presence of poly(ethylene glycol) with an enzyme catalyst, a lipase from Candida antarctica, Pseudomonas cepacia, or Pseudomonas fluorescens. The influence of several parameters, including time, temperature, and enzyme and monomer concentration, on the polymerization rate was studied. The resulting polymers were characterized by ¹H-NMR or ¹³C-NMR, Fourier transform infrared spectroscopy, matrix-assisted laser desorption/ionization–time of flight mass spectroscopy, and gel permeation chromatography. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Poly(methyl methacrylate)/poly(ethylene glycol)/poly(ethylene glycol dimethacrylate) micelles: Preparation,characterization, and application as doxorubicin carriers

A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and ¹H‐NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self‐assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug‐loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug‐loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug‐loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39623.     

Syntheses of poly(lactic acid)‐poly(ethylene glycol) serial biodegradable polymer materials via direct melt polycondensation and their characterization

Directly starting from lactic acid (LA) and poly(ethylene glycol) (PEG), biodegradable material polylactic acid‐polyethylene glycol (PLEG) was synthesized via melt copolycondensation. The optimal synthetic conditions, including prepolymerization method, catalyst kinds and quantity, copolymerization temperature and time, LA stereochemical configuration, feed weight ratio m_LA/m_PEG and M_n of PEG, were all discussed in detail. When D ,L ‐LA and PEG (M_n = 1000 Da) prepolymerized together as feed weight ratio m_{D ,l‐LA}/m_PEG = 90/10, 15 h copolycondensation under 165°C and 70 Pa, and 0.5 wt % SnO as catalyst, gave D ,L ‐PLEG1000 with the highest [η] of 0.40 dL/g, and the corresponding MW was 41,700 Da. Using L ‐LA instead of D ,L ‐LA, 10 h polymerization under 165°C and 70 Pa, and 0.5 wt % SnO as catalyst, gave L ‐PLEG1000 with the highest [η] of 0.21 dL/g and MW of 15,600 Da. Serial D ,L ‐PLEG with different feed weight ratio and M_n of PEG were synthesized via the simple and practical direct melt copolycondensation, and characterized with FTIR, ¹H NMR, GPC, DSC, XRD, and contact angle testing. D ,L ‐PELG not only had higher MW than PDLLA, PLLA and L ‐PELG, but also better hydrophilicity than PDLLA. The novel one‐step method could be an alternative route to the synthesis of hydrophilic drug delivery carrier PLEG instead of the traditional two‐step method using lactide as intermediate. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 577–587, 2006     

Novel mucoadhesive polymer: Synthesis and mucoadhesion of poly[acrylic acid‐co‐poly(ethylene glycol) monomethylether monomethacrylate‐co‐dimethylaminoethyl methacrylate]

This study was to design a mucoadhesive based on the biological and physicochemical properties of the buccal mucosa to achieve optimal mucoadhesion in the aqueous buccal environment. Since the buccal surface is negatively charged, a series of novel mucoadhesive poly[acrylic acid‐co‐poly(ethylene glycol) monomethylether monomethacrylate‐co‐dimethylaminoethyl methacrylate] [poly (AA‐PEGMM‐DMEMA)] were synthesized by incorporating the cationic monomer DMEMA into poly(AA‐PEGMM) to enhance the interactions between the mucohadhesive polymer and the buccal mucosa. The compositions of poly(AA‐PEGMM‐DMEMA) were varied by changing the content of DMEMA from 0 to 4.8 mol % while keeping the mole ratio of AA to PEGMM at a constant 9 : 1. It was found that the force of mucoadhesion of poly(AA‐PEGMM‐DMEMA) increased initially, as DMEMA content increased, and reached the maximum at 1% of DMEMA. Further increasing the content of DMEMA decreased the mucoadhesion. The polymers with 0.5 to 2.9% DMEMA appeared to have maximum mucoadhesion after prehydration for 5 min. An ATR–FTIR spectroscopy study revealed that intrapolymer interactions and intersurface interactions played opposite roles in the mucoadhesion performance of the polymers. Optimal mucoadhesion can be achieved by balancing these two interactions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94:2431–2437, 2004     

Modification of ibuprofen drug release from poly(ethylene glycol) layered silicate nanocomposites prepared by hot‐melt extrusion

Composites of the poorly water soluble drug ibuprofen, a nonsteroidal anti‐inflammatory commonly used for pain relief, with layered silicates (nanoclays) and a poly(ethylene glycol) (PEG) were prepared by hot melt extrusion. A highly intercalated and partially exfoliated morphology was determined using wide‐angle x‐ray diffraction, field emission scanning electron microscopy, and high‐resolution transmission electron microscopy. The crystalline content of PEG was significantly reduced, as shown by differential scanning calorimetry studies, as a consequence of the large surface area of clay platelets physically hindering polymer chain dynamics and, in the case of montmorillonite, by tethering of PEG via hydrogen bonding. Addition of layered silicate retarded the release of ibuprofen from the PEG matrix, even though the crystalline content of PEG was reduced. This study therefore indicates that drug release in solid dispersion systems may be modified or indeed tailored by the inclusion of layered silicates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40284.     

Kinetics study of isothermal nicotine release from poly(acrylic acid) hydrogel

The isothermal kinetic of the release of nicotine from a poly(acrylic acid) (PAA) hydrogel was investigated at temperature range from 26°C to 45°C. Specific shape parameters of the kinetic curves, the period of linearity and saturation time were determined. The change in the specific shape parameters of the kinetic curves with temperature and the kinetic parameters of release of nicotine E_a and ln A were determined. By applying the “model fitting” method it was established that the kinetic model of release of nicotine from the PAA hydrogel was [1 − (1 − α)^1/3] = k_Mt. The limiting stage of the kinetics release of nicotine was found to be the contracting volume of the interaction interface. The distribution function of the activation energy was determined and the most probable values of activation energies of 25.5 kJ mol⁻¹ and 35 kJ mol⁻¹ were obtained. Energetically heterogeneity of the interaction interface was explained by the existence of the two different modes of bonding the nicotine molecules onto the hydrogel network by hydrogen bond and electrostatic forces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis,characterization, and drug release activity of structurally modified poly(vinyl alcohol)

The main aim of the present investigation is synthesis of drug‐grafted poly(vinyl alcohol) (PVA) for sustainable drug release in order to avoid bulk release and unwanted side effects. Here, the PVA was structurally modified with five different drug molecules in DMSO medium at 85 °C under N₂ atmosphere for 2 h. The structure of modified PVA was confirmed by FTIR and ¹H NMR spectra and further it was characterized by TGA, DSC, and SEM. The tensile strength and % elongation for the structurally modified PVA were determined. The FTIR spectrum showed peaks corresponding to the C?O and C? S stretching due to the grafted drug molecules. The ¹H NMR spectrum showed the acrylic CH₂ proton signal of PVA around 1.6 ppm. The SEM showed different surface morphology for the structurally modified PVA. The mechanical properties of the structurally modified PVA was found to be reduced due to the presence of traces of solvent molecules and the breaking of inter‐ and intramolecular hydrogen bonding. The sustainable drug release through hydrolysis mechanism was tested at the pH of 7.3. Generally, the drug release followed the Korsmeyer–Peppas model with Fickian drug transportation mechanism except Furosemide (Fur)‐grafted PVA system at the pH of 7.3. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46620.     

Effects of pore morphology and size on antimicrobial activity of chitosan/poly(ethylene glycol) diacrylate macromer semi‐IPN hydrogels

The objective of this study was to obtain antibacterial active chitosan/poly(ethylene glycol) diacrylate macromere (CS/PEGM) semi‐IPN hydrogels near a neutral pH level by changing their pore size and morphology. These hydrogels were prepared from CS and PEGM with different molecular weights in the presence of pore‐forming agents, poly (ethylene glycol) (PEG) or sodium bicarbonate (NaHCO₃), by using two different initiator system, namely chemical or UV. A combination of CS with PEG or NaHCO₃ in the presence of PEGM could be able to create desired pore formation in both initiator systems. The antibacterial activity of hydrogels changed with the molecular weight (g/mol) of PEGM in the order 2000>400>8000. A chemical initiation system was found more suitable than the UV initiation system for antibacterial activity. Hydrogels showing the highest antibacterial activity on Staphylococcus aureus and Escherichia coli have medium or distributed pore size and interconnected pores. Hydrogels prepared with PEGM (M_n: 2000 g/mol) were proposed for antibacterial wound dressing and soft tissue regeneration applications owing to their antibacterial activity and elastic modulus. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42707.     

Fluorescent microspheres of poly(ethylene glycol)–poly(lactic acid)–fluorescein copolymers synthesized by Ugi four‐component condensation

Microparticles formed by poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) diblock copolymers containing fluorescein grafted to the polymer chain were synthesized by a Ugi four‐component condensation (UFCC) reaction. To synthesize these copolymers, lactide was first polymerized by a ring‐opening polymerization with alcohol initiators containing functional groups to give carboxyl‐ and aldehyde‐end‐functionalized PLA. Two different fluorescent block copolymers (FCPs) of PEG–PLA conjugated to fluorescein (FCP 1 and FCP 2) were then synthesized by UFCC; they gave yields in the range 65–75%. These copolymers were characterized well according their chemical structures and thermal properties, and we prepared fluorescent microspheres (FMSs) from them with the single emulsion–solvent evaporation method (FMS 1 and FMS 2). A new application of UFCC in the preparation of biomasked drug‐delivery systems is proposed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42994.     

In vitro evaluation of efficacy of dihydroartemisinin‐loaded methoxy poly(ethylene glycol)/poly(l‐lactic acid) amphiphilic block copolymeric micelles

Dihydroartemisinin (DHA)‐loaded methoxy poly(ethylene glycol)/poly(l ‐lactic acid) (mPEG₅₀₀₀—PLLA₃₂₀₀) amphiphilic block copolymeric micelles (DHA‐CM) have been prepared using modified solvent evaporation method. Physicochemical properties of DHA‐CM were investigated by using dynamic light scattering, transmission electron microscopy, high‐performance liquid chromatography, and Fourier transform infrared. Polymers formed stable, spherical, and worm‐like micelles with mean sizes smaller than 130 nm. In vitro release experiments revealed that DHA‐CM provided a more solubilizing effect than DHA suspension; in addition, it was showed that drug release profiles highly depended on pH values of dissolution media. Various types of lyoprotectants were tested to improve the redispersion performance of the freeze‐dried products. 3‐(4, 5‐dimethyl‐ thiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide assay was used to evaluate the cytotoxicity of micellar solutions of freeze‐dried DHA‐CM. The results showed that the IC₅₀ values of DHA‐CM and DHA suspension for KB cell lines were 18.70 and 24.55 μM, respectively. However, DHA‐CM had little cytotoxicity for L02 cell lines. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Iodine-loaded poly(silicic acid) gellan nanocomposite mucoadhesive film for antibacterial application

Iodine-loaded poly(silicic acid) gellan nanocomposite film was fabricated and evaluated for antibacterial properties. Poly(silicic acid) nanoparticles were synthesized by condensation of silicic acid under alkaline conditions in the presence of polyvinyl pyrrolidone, phosphate ions, and molecular iodine. The nanoparticles were incorporated into gellan dispersion to prepare gellan nanocomposite film using the solvent casting method. The nanocomposite films were characterized by Fourier transformed infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction studies. The results of characterization studies indicated improved thermal stability and an increase in the degree of crystallinity. The scanning electron micrographs and energy dispersive X-ray spectrum confirmed the uniform dispersion of silica and iodine in the nanocomposite films. The analysis of physical and mechanical properties revealed the enhanced tensile strength, moisture resistance, and higher folding endurance of poly(silicic acid) gellan nanocomposite films as compared to gellan film. Further, the iodine-loaded poly(silicic acid) gellan nanocomposite films showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and effective mucoadhesive strength. The results indicate that iodine-loaded poly(silicic acid) gellan nanocomposite mucoadhesive film can be used for potential antibacterial applications in pharmaceuticals.