Preadsorption of polymers on glass and silica to reduce fibrinogen adsorption

Glass and silica beads were precoated with various polymers to obtain steric exclusion chromatography (SEC) supports which are nonadsorbant for hydrophilic macromolecules. The efficiency of this treatment was estimated by subsequent radiolabeled fibrinogen adsorption. The result obtained with a block copolymer was better than with various hydrophilic homopolymers. This ABA type block copolymer, where A is a poly(N-acetylethyleneimine) (PAEI) sequence and B a polyethylene oxide (PEO) sequence was preadsorbed at pH 4.5 and 25 degrees C; the fibrinogen adsorption was reduced to less than 5% of the value observed on untreated solid surfaces. Thus the hemocompatibility of solid supports should be increased by precoating with this block copolymer. Results for nonporous glass beads and porous silica particles were in good correlation.     

Double Hydrophilic Poly(ethylene oxide)‐block‐Poly(dehydroalanine) Block Copolymers: Comparison of Two Different Synthetic Routes

Two different synthetic pathways give access to the amphiphilic block copolymer poly(ethylene oxide)‐block‐poly(tert‐butoxycarbonylaminomethylacrylate). In the first approach, two end‐functionalized segments are linked via click chemistry; and in the second approach, a poly(ethylene oxide) (PEO) based macroinitiator is chain extended via atom transfer radical polymerization (ATRP). In both cases the linking unit consists of an amide group, which is necessary to effectively deprotect the corresponding polymer precursor without cleavage of both segments. For this, amide‐containing ATRP initiators are employed and successful synthesis by nuclear magnetic resonance (NMR) and size exclusion chromatography (SEC) analyses before comparing both pathways is demonstrated. After deprotection, a novel double hydrophilic block copolymer, poly(ethylene oxide)‐block‐poly(dehydroalanine), is obtained, which is investigated using SEC (aqueous and DMSO) and ¹H‐NMR spectroscopy. Containing a potentially zwitterionic PDha segment and a high density of both amino and carboxylic groups, pH‐dependent aggregation of the block copolymer is expected and is studied using dynamic light scattering, revealing interesting solution properties. The corresponding polymers are applied in various areas including drug delivery systems or in biomineralization.     

Détermination des masses et des distributions moléculaires d'un poly(aryléthercétone-co-sulfone) semi-cristallin (HTX) à l'aide d'une méthode de dérivatisation chimique, 2. Chromatographie d'exclusion stérique du HTX sulfoné

HTX, a poly(aryletherketone-co-sulfone), is characterized by size exclusion chromatography (SEC) at room temperature. As HTX is not soluble in any solvent compatible with the SEC instrumentation, a derivatization procedure is applied in order to prepare a modified copolymer with improved solubility properties. This derivatization consists in a sulfonation by concentrated sulfuric acid. The derivative polymer is soluble in N-methyl-2-pyrrolidone (NMP), a classical SEC solvent. Sulfonated HTX (HTXS) is a polyelectrolyte. Consequently, a salt is added to NMP to perform reliable viscometric and SEC analyses. The SEC method is standardized with the establishment of the universal calibration with poly(methyl methacrylate) standards and the determination of the Mark-Houwink-Sakurada relationship of HTXS in NMP-salt at 25°C. Finally, the reliability of the derivatization procedure and of the SEC method is confirmed by comparison with molecular masses from NMR.     

Synthesis and molecular weight characterization of low molecular weight end-functionalized poly(4-acryloylmorpholine)

New amphiphilic oligomers ending at one side with a reactive function were synthesized by radical polymerization of a vinyl monomer, N-acryloylmorpholine, in the presence of functionalized chain-transfer agents (CTAs). The oligomers were characterized in terms of molecular weight and molecular weight distribution, by means of analytical size-exclusion chromatography (SEC) working in buffered aqueous media. This has been accomplished by determining a calibration curve for a set of SEC columns, with poly(N-acryloylmorpholine) standards purposely obtained by means of preparative SEC. The transfer constant C_T of some CTAs towards N-acryloylmorpholine has been estimated to be approximately 1.     

Effect of molecular weight of amine end-modified poly(β-amino ester)s on gene delivery efficiency and toxicity

Amine end-modified poly(β-amino ester)s (PBAEs) have generated interest as efficient, biodegradable polymeric carriers for plasmid DNA (pDNA). For cationic, non-degradable polymers, such as polyethylenimine (PEI), the polymer molecular weight (MW) and molecular weight distribution (MWD) significantly affect transfection activity and cytotoxicity. The effect of MW on DNA transfection activity for PBAEs has been less well studied. We applied two strategies to obtain amine end-modified PBAEs varying in MW. In one approach, we synthesized four amine end-modified PBAEs with each at 15 different monomer molar ratios, and observed that polymers of intermediate length mediated optimal DNA transfection in HeLa cells. Biophysical characterization of these feed ratio variants suggested that optimal performance was related to higher DNA complexation efficiency and smaller nanoparticle size, but not to nanoparticle charge. In a second approach, we used preparative size exclusion chromatography (SEC) to obtain well-defined, monodisperse polymer fractions. We observed that the transfection activities of size-fractionated PBAEs generally increased with MW, a trend that was weakly associated with an increase in DNA binding efficiency. Furthermore, this approach allowed for the isolation of polymer fractions with greater transfection potency than the starting material. For researchers working with gene delivery polymers synthesized by step-growth polymerization, our data highlight the potentially broad utility of preparative SEC to isolate monodisperse polymers with improved properties. Overall, these results help to elucidate the influence of polymer MWD on nucleic acid delivery and provide insight toward the rational design of next-generation materials for gene therapy.     

Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

Folate-conjugated amphiphilic hyperbranched block copolymer (H40–PLA-b-MPEG/PEG–FA) with a dendritic Boltorn^® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell and a hydrophilic methoxy poly(ethylene glycol) (MPEG) and folate-conjugated poly(ethylene glycol) (PEG–FA) outer shell was synthesized as a carrier for tumor-targeted drug delivery. The block copolymer was characterized using ¹H NMR and gel permeation chromatography (GPC) analysis. Due to its core–shell structure, this block polymer forms unimolecular micelles in aqueous solutions. The micellar properties of H40–PLA-b-MPEG/PEG–FA block copolymer were extensively studied by dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). An anticancer drug, doxorubicin in the free base form (DOX) was encapsulated into H40–PLA-b-MPEG/PEG–FA micelles. The DOX-loaded micelles provided an initial burst release (up to 4 h) followed by a sustained release of the entrapped DOX over a period of about 40 h. Cellular uptake of the DOX-loaded H40–PLA-b-MPEG/PEG–FA micelles was found to be higher than that of the DOX-loaded H40–PLA-b-MPEG micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. In vitro degradation studies revealed that the H40–PLA-b-MPEG/PEG–FA block copolymer hydrolytically degraded into polymer fragments within six weeks. These results indicated that the micelles prepared from the H40–PLA-b-MPEG/PEG–FA block copolymer have great potential as tumor-targeted drug delivery nanocarriers.     

Hydrolytic degradation and protein release studies of thermogelling polyurethane copolymers consisting of poly[(R)-3-hydroxybutyrate], poly(ethylene glycol), and poly(propylene glycol)

This paper reports the hydrolytic degradation and protein release studies for a series of newly synthesized thermogelling tri-component multi-block poly(ether ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB), poly(propylene glycol) (PPG), and poly(ethylene glycol) (PEG). The poly(PEG/PPG/PHB urethane) copolymer hydrogels were hydrolytically degraded in phosphate buffer at pH 7.4 and 37 degrees C for a period of up to 6 months. The mass loss profiles of the copolymer hydrogels were obtained. The hydrogel residues at different time periods of hydrolysis were visualized by scanning electron microscopy, which exhibited increasing porosity with time of hydrolysis. The degradation products in the buffer were characterized by GPC, (1)H NMR, MALDI-TOF, and TGA. The results showed that the ester backbone bonds of the PHB segments were broken by random chain scission, resulting in a decrease in the molecular weight. In addition, the constituents of degradation products were found to be 3-hydroxybutyric acid monomer and oligomers of various lengths (n=1-5). The protein release profiles of the copolymer hydrogels were obtained using BSA as model protein. The results showed that the release rate was controllable by varying the composition of the poly(ether ester urethane)s or by adjusting the concentration of the copolymer in the hydrogels. Finally, we studied the correlation between the protein release characteristics of the hydrogels and their hydrolytic degradation. This is the first example that such a correlation has been attempted for a biodegradable thermogelling copolymer system.     

Synthesis and characterization of PEG-coated poly(ethyl cyanoacrylate) nanoparticles

INTRODUCTION　　 Recently,as drug delivery,colloidal polymeric systems have gained a lot ofattention〔1〕. They were able to prevent drug degradation,control its release andachieve specific targeting.However polymeric nanoparticles were eliminated fromthe bloodstream by the macrophages of the mononuclear phagocyte system(MPS)within seconds orminites. Itisreported thatnanoparticlesattaching hydrophilicandflexible,such as poly(ethylene glycol) (PEG) can dramatically increase bloodcirculat…     

Tissue anti-adhesion potential of ibuprofen-loaded PLLA-PEG diblock copolymer films

This study was designed to evaluate the effect of polyethylene glycol (PEG) and nonsteroidal anti-inflammatory drug (ibuprofen) on the prevention of postsurgical tissue adhesion. For this, poly(L-lactic acid) (PLLA)-PEG diblock copolymers were synthesized by ring opening polymerization of L-lactide and methoxy polyethylene glycol (Mw 5000) of different compositions. The synthesized copolymers were characterized by gel permeation chromatography and 1H-nuclear magnetic resonance spectroscopy. PLLA-PEG copolymer films were prepared by solvent casting. The prepared copolymer films were more flexible and hydrophilic than the control PLLA film, as investigated by the measurements of glass transition temperature, water absorption content, and water contact angle. The drug release behavior from the ibuprofen (10 wt%)-loaded copolymer films was examined by high performance liquid chromatography. It was observed that the drug was released gradually up to about 40% of total loading amount after 20 days, depending on PEG composition; more drug release from the films with higher PEG compositions. In vitro cell adhesions on the copolymer films with/without drug were compared by the culture of NIH/3T3 mouse embryo fibroblasts on the surfaces. For in vivo evaluation of tissue anti-adhesion potential, the copolymer films with/without drug were implanted between the cecum and peritoneal wall defects of rats and their tissue adhesion extents were compared. It was observed that the ibuprofen-containing PLLA-PEG films with high PEG composition (particularly PLLA113-PEG113 film with PEG composition, 50 mol%) were very effective in preventing cell or tissue adhesion on the film surfaces, probably owing to the synergistic effects of highly mobile, hydrophilic PEG and anti-inflammatory drug, ibuprofen.     

Biodegradable poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether diblock copolymers: structures and surface properties relevant to their use as biomaterials

To obtain biodegradable polymers with variable surface properties for tissue culture applications, poly(ethylene glycol) blocks were attached to poly(lactic acid) blocks in a variety of combinations. The resulting poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether (Me.PEG-PLA) diblock copolymers were subject to comprehensive investigations concerning their bulk microstructure and surface properties to evaluate their suitability for drug delivery applications as well as for the manufacture of scaffolds in tissue engineering. Results obtained from 1H-NMR, gel permeation chromatography, wide angle X-ray diffraction and modulated differential scanning calorimetry revealed that the polymer bulk microstructure contains poly(ethylene glycol)-monomethyl ether (Me.PEG) domains segregated from poly(D,L-lactic acid) (PLA) domains varying with the composition of the diblock copolymers. Analysis of the surface of polymer films with atomic force microscopy and X-ray photoelectron spectroscopy indicated that there is a variable amount of Me.PEG chains present on the polymer surface, depending on the polymer composition. It could be shown that the presence of Me.PEG chains in the polymer surface had a suppressive effect on the adsorption of two model peptides (salmon calcitonin and human atrial natriuretic peptide). The possibility to modify polymer bulk microstructure as well as surface properties by variation of the copolymer composition is a prerequisite for their efficient use in the fields of drug delivery and tissue engineering.     

聚谷氨酸苄酯/聚乙二醇/聚谷氨酸苄酯嵌段共聚物膜的生物降解性

以木瓜蛋白酶(papain)做蛋白水解酶,通过测定酶解前后聚谷氨酸苄酯/聚乙二醇/聚谷氨酸苄酯(PBLG/PEG/PBLG)嵌段共聚物膜的重量和分子量的变化来研究其体外生物降解规律.结果表明,共聚物的分子量及PEG嵌段的含量影响它们的降解速度.共聚物的分子量越大,其降解速度越慢.PEG含量越高,共聚物的水溶胀率越大,而共聚物的水溶胀率越大,其降解速度越快.通过调节共聚物中PEG的含量和共聚物的分子量可以控制共聚物的降解速度.     

Effect of polymer architecture on surface properties, plasma protein adsorption, and cellular interactions of pegylated nanoparticles

The aim of the present study was to evaluate the cellular interaction of nanoparticles (NPs) prepared from different pegylated polymers and elucidate the effect of polymer architecture, for instance, grafted versus block copolymer on their cellular uptake. Fluorescein-labeled NPs of four different polymers, viz., poly(D,L-lactide) (PLA), poly(ethylene glycol)(1%)-graft-poly(D,L-lactide) (PEG(1%)-g-PLA), poly(ethylene glycol)(5%)-graft-poly(D,L-lactide) (PEG(5%)-g-PLA), and (poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly(D,L-lactide))(n) multiblock copolymer (PLA-PEG-PLA)(n) were prepared. These NPs were characterized for their size, zeta-potential, and surface morphology. XPS studies revealed possibility of chemical interaction between PLA-COOH groups and PVA-OH groups, thus making it difficult to be washed off the NP surface completely. Grafted polymer NPs showed more surface PEG coverage than (PLA-PEG-PLA)(n) despite of their comparatively lower PEG content. The results of surface properties were translated into protein binding showing least amount of proteins bound to grafted copolymer NPs as against multiblock copolymer NPs. NPs showed no toxicity to RAW 264.7 cells. Cellular uptake of NPs was temperature and concentration-dependent as well as involved clathrin-mediated processes. Thus, this study confirms the importance of polymer architecture in determining the surface properties and hence, protein binding and cellular interactions of NPs. Also, it was shown that grafted copolymer NPs reduced macrophage uptake as compared to multiblock copolymer although mechanisms different than phagocytosis were involved.     

Effects of soft segments and hydrolysis on the crystallization behavior of degradable poly(oxyethylene)/poly(L-lactide) block copolymers

The crystallization behavior of poly(oxyethylene) (PEG)/poly(L -lactide) (PLLA) block copolymers with PEG (number-average molecular weights M _n = 1000–6000) contents ≦ 18,3 wt.-% has been studied under different isothermal temperature and linear cooling conditions. A differential scanning calorimeter was used to monitor the energetics of the crystallization process from the melt state. The influence of copolymer composition and hydrolysis on radial growth rates of spherulites, G, in PEG/PLLA copolymer was investigated using polarized light video-microscopy. The data were analyzed in terms of a model describing two processes, namely crystal nucleation and growth which were observed experimentally in a typical Avrami plot for the isothermal data. At a given crystallization temperature, G's are increased with increasing PEG content and with decreasing PEG segment length in PEG/PLLA copolymer spherulites. The Avrami exponent n and rate coefficient k of PEG/PLLA copolymers decrease with increasing hydrolysis time up to 200 h. The spherulite morphology appeared to be a complex function of copolymer composition, hydrolysis time and crystallization temperature.     

Bilayered biodegradable poly(ethylene glycol)/poly(butylene terephthalate) copolymer (Polyactive) as substrate for human fibroblasts and keratinocytes.

The purpose of this study was to find an optimal polymer matrix and to optimize the culture conditions for human keratinocytes and fibroblasts for the development of a human skin substitute. For this purpose porous, dense bilayers made of a block copolymer of poly(ethylene glycol terephthalate) (PEGT) and poly(butylene terephthalate) (PBT; Polyactivetrade mark) with a PEGT/PBT weight ratio of 55/45 and a PEG molecular weight (MW) of 300, 600, 1000, or 4000 Da were used. The best performance was achieved with PEGT/PBT copolymer with MW of PEG 300 D (300PEG55PBT45). When fibroblasts were seeded into the porous underlayer and cultured for 3 weeks in medium supplemented with 100 microg/mL ascorbic acid, all pores were filled with fibroblasts and with extracellular matrix, which was judged from the presence of collagen types I, III, and IV, and laminin. When seeded onto the dense top layer of the bilayered (cell free or fibroblast populated) copolymer matrix, human keratinocytes grew out into confluent sheets. After subsequent lifting to the air-liquid interface, a multilayered epithelium with a morphology corresponding to that of the native epidermis was formed. Some differences could still be observed: the expression and localization of some differentiation specific proteins was different and close to that seen in hyperproliferative epidermis; a basal lamina and anchoring zone were absent.     

Molecular Mass Characteristics of (2‐Benzothiazolon‐3‐yl)acetic Acid–Telechelic Poly(ethylene oxide)s Determined by MALDI‐TOF Mass Spectrometry and SEC

(2‐benzothiazolon‐3‐yl)acetic acid–telechelic poly(ethylene oxide)s (1 100–4 440 Da) with narrow molecular mass distributions (MMD) were analysed by matrix‐assisted laser desorption‐ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) and size exclusion chromatography (SEC). The average molecular masses (M̄_n and M̄_w) determined by both methods were compared and a good agreement established. The cutting of the low molecular part of the initial poly(ethylene glycol) MMD during purification and isolation of the produced telechelic poly(ethylene oxide)s was proved. For this reason, the degree of esterification (x) of poly(ethylene glycol) (PEG) with (2‐benzothiazolon‐3‐yl)acetic acid was calculated by MALDI‐TOF MS and SEC, using additional UV data. The two series of x values derived from the M̄_n‐values, determined by the two methods, are very close. All of them are less than unity and the differences between the two types of x values decrease with the PEG molecular mass growth.     

Polyethylenimine-grafted copolymer of poly(l-lysine) and poly(ethylene glycol) for gene delivery

A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI) with low molecular weight was grafted onto the block copolymer (PPL) of poly(l-lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b-PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG blocks were expected to render the vector biodegradability, proton buffering capacity, low cationic toxicity and potentially long circulation in vivo, respectively. Given proper control of molecular composition, the copolymers demonstrated lower cytotoxicity, proton buffering capacity, ability to condense pDNA and mediate effective gene transfection in various cell lines. With folate as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher transgene activity than its nontargeting counterpart for both reporter and therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL) in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression of cell viability. Our results indicate that the copolymers might be a promising vector combining low cytotoxicity, biodegradability, and high gene transfection efficiency.     

Sterically blocking adhesion of cells to biological surfaces with a surface-active copolymer containing poly(ethylene glycol) and phenylboronic acid.

Graft copolymers were designed that could spontaneously bind to biological surfaces and block subsequent recognition and adhesion at those surfaces. Phenylboronic acid (PBA) moieties in the polymer backbone provided binding to surfaces, forming reversible covalent complexes with cis-diols found in many biological molecules. Pendant poly(ethylene glycol) (PEG) side chains sterically protected those surfaces from subsequent interactions with other proteins and cells. The PEG and PBA grafting ratios on these poly-L-lysine-graft-(PEG;PBA) copolymers [PLL-g-(PEG;PBA)] were varied, and the polymers were tested in models relevant to undesirable wound-healing responses such as peritoneal adhesion formation and posterior capsule opacification. PLL-g-(PEG;PBA) polymers spontaneously coated tissue culture polystyrene and completely blocked rabbit lens epithelial cell adhesion to the surface over a wide range of PEG grafting ratios. PLL-g-(PEG;PBA)s with optimal grafting ratios were able to coat adsorbed serum proteins or extracellular matrices and block cell spreading on the surfaces at 4 h, although the effect was lost within 24 h. The polymer also enhanced the efficacy of surgical lysis of peritoneal adhesions in rats. The reversible covalent complexes formed by the PBA moieties on the copolymer backbone were more effective at binding biological surfaces than electrostatic interactions formed via a copolymer lacking the PBA moieties, that is, PLL-g-PEG.     

Thermo- and pH-responsive copolymers based on PLGA-PEG-PLGA and poly(l-histidine): Synthesis and in vitro characterization of copolymer micelles

A series of novel thermo- and pH-responsive block copolymers of PHis-PLGA-PEG-PLGA-PHis composed of poly(ethylene glycol) (PEG), poly(d,l-lactide-co-glycolide) (PLGA) and poly(l-histidine) (PHis) were synthesized and used for the construction of stimuli-responsive copolymer micelles. The starting polymers of PLGA-PEG-PLGA and PHis were synthesized by ring-opening polymerization of dl-lactide and glycolide with PEG as an initiator and l-histidine N-carboxylanhydride with isopropylamine as an initiator, respectively. The final copolymer was obtained by the coupling reaction of PHis with PLGA-PEG-PLGA. The copolymer micelles were constructed to have an inner core consisting of two hydrophobic blocks (PLGA and deprotonated PHis) and an outer hydrophilic PEG shell. The temperature- and pH-induced structure changes of the micelles were characterized by an alteration in particle size, a decrease in pyrene florescence intensity, and a variation of ¹H NMR spectra in D₂O. It was speculated that the hydrophobic–hydrophilic transitions of PEG and PHis in response to temperature and pH variations accounted for the destabilization of micelles. In vitro release profiles, cell cytotoxicity and intracellular location studies further confirmed the temperature- and pH-responsive properties of the copolymer micelles. These results demonstrate the potential of the developed copolymers to be stimuli-responsive carriers for targeted delivery of anti-cancer drugs.     

The in vitro hydrolysis of poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol)

This paper reports the study of the complete degradation process for a series of newly synthesized multi-block poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB) as hard and hydrophobic block and poly(ethylene glycol) (PEG) as soft and hydrophilic segment. The initial stages of degradation of the poly(PHB/PEG urethane)s were monitored by carrying out the degradation experiments at pH 7.4 and 37 degrees C. The weight loss of the copolymer films was traced, and the degraded copolymer films were characterized by GPC, (1)H NMR, TGA, and SEM. The induction phase of the polymer degradation was characterized by a random chain scission of the ester backbone bonds of the PHB segments and an insignificant decline in the weight of the polymer films. An accelerated degradation process was carried out at pH 11.5 and 37 degrees C to investigate the long-term degradation behaviour. The characterization of the degraded polymer films was similar to that for the experiment at pH 7.4. In addition, the water-soluble degradation products were characterized by GPC, (1)H NMR, and FTIR. The main components of the water-soluble degradation products were found to be PEG blocks (monomeric up to quadmeric), 3-hydroxybutyric acid, and crotonic acid. It was found that the copolymer incorporating the highest amount of PEG degraded at the highest rate of all the copolymers studied. The complete degradation of the poly(PHB/PEG urethane)s was monitored using a combination of the physiological and accelerated hydrolytic degradation.     

Complex formation of polyampholyte with proton-accepting polymers through hydrogen bonding

Polyampholytes, copolymers of methacrylic acid and 2-dimethylaminoethyl methacrylate [C(MA-AM)x] of various composition, were synthesized. Their isoelectric points (pI) are in the range 5 < pH < 7. Undissociated methacrylic acid residues in the copolymers can interact with ether oxygens of poly(ethylene glycol) (PEG) and ketone groups of poly(N-vinyl-2-pyrrolidone) (PVPo) in the acidic pH region through hydrogen bonding. However, only copolymers having more than about 60 mol-% of methacrylic acid residues form complexes with PVPo and high molecular weight PEG. The composition of the obtained complexes is 1:1 (mole ratio of methacrylic acid residues of the copolymer to repeating units of PVPo and PEG).