Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures.

Starch-g-poly(acrylic acid) copolymers or grafted starches synthesized by 60Co irradiation or chemical modification and co-freeze-dried starch/poly(acrylic acid) mixtures were evaluated on their ex vivo bioadhesion capacity. The buccal absorption of testosterone from a bioadhesive tablet formulated with the grafted starches or starch/poly(acrylic acid) mixtures was investigated. The results were compared to a reference formulation (physical mixture of 5% Carbopol 974P and 95% Drum Dried Waxy Maize). Rice starch-based irradiated grafted starches showed the best bioadhesion results. Partial neutralization of the acrylic acid with Ca(2+) ions resulted in significantly higher bioadhesion values compared to the reference. Ca(2+) and Mg(2+) partially neutralized maltodextrin-based irradiated grafted starches showed significantly higher bioadhesion values compared to the reference formulation. The chemically modified grafted starches showed significantly higher adhesion force values than for the reference tablet. None of the co-freeze-dried starch/poly(acrylic acid) mixtures showed significantly higher bioadhesion results than the reference (Bonferroni test, P<0.05). A chemically modified grafted starch could sustain the 3 ng/ml plasma testosterone target concentration during +/- 8 h (T(>3 ng/ml)). By lyophilization of a partially neutralized irradiated grafted starch, the in vivo adhesion time (22.0 +/- 7.2 h) and the T(>3 ng/ml) (13.5 +/- 1.3 h) could be increased. The absolute bioavailability of the lyophilized formulation approached the reference formulation. Some of the grafted starches showed to be promising buccal bioadhesive drug carriers for systemic delivery.     

Optimisation of an in vitro procedure for the determination of the enzymatic inhibition potency of multifunctional polymers.

An in vitro procedure for the determination of the inhibition potency of multifunctional polymers towards the proteolytic enzyme trypsin was optimised. Carbopol((R)) 934P was used as the reference polymer. The enzymatic reaction was optimised and the HPLC method was validated. The optimal substrate concentration and enzymatic activity were determined aiming at extracting the linear or steady-state part of the metabolite concentration versus time curve of the enzymatic degradation reaction. A substrate concentration of 20 mmol/l N-alpha-benzoyl-L-arginine-ethylester and an enzymatic activity of 30 enzymatic units trypsin/ml were used. The degree of trypsin inhibition was expressed by the inhibition factor (IF), defined as the ratio of the enzymatic reaction rate without a polymer (control) to the reaction rate in the presence of a polymer. During the optimisation of the trypsin inhibition assay, formation of an ion complex between the substrate and the poly(acrylic acid) was observed. The complex formation was concentration dependent, but the influence on the enzymatic reaction was negligible as long as an excessive substrate concentration was present in the reaction medium. The optimised method allows to characterize, evaluate and compare the in vitro trypsin inhibition strength for most multifunctional polymers.     

Evaluation of the mucosal irritation potency of co-spray dried Amioca/poly(acrylic acid) and Amioca/Carbopol 974P mixtures.

The purpose of this study was to evaluate the biocompatibility of different Amioca/poly(acrylic acid) and Amioca/Carbopol 974P co-spray dried mixtures with an alternative mucosal irritation test using slugs. The irritation potential of the mixtures was measured by the amount of mucus produced during a repeated 30-min contact period. Additionally, membrane damage was assessed by measuring the protein and enzyme release from the body wall of slugs after treatment. All the Amioca/poly(acrylic acid) co-spray dried mixtures (50:50 and 25:75 ratios) induced slight irritation of the mucosal tissue as was demonstrated by the significantly increased mucus production however no increased protein and enzyme release was detected. Co-spray dried Amioca/Carbopol 974P mixtures containing 40% and more Carbopol 974P demonstrated a significantly higher mucus production and release of cytosolic LDH, indicating membrane damage. The total mucus production of the slugs treated with the co-spray dried mixtures containing up to 20% Carbopol 974P was significantly higher compared to the blank slugs. However, these mixtures induced no membrane damage since no additional effect on the protein release and no enzyme release was detected. By co-spray drying up to 20% Carbopol 974P could be incorporated without showing a distinct sign of irritation. These mixtures can be considered as potentially safe bioadhesive carriers.     

Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization.

To develop a new mucoadhesive drug carrier, poly(vinyl pyrrolidone) (PVP)/poly(acrylic acid) (PAA) interpolymer complexes were prepared by the template polymerization of acrylic acid using PVP as a template polymer. Fourier transform infrared results showed that the interpolymer complexes were formed by hydrogen bonds between the carboxyl groups of PAA and the carbonyl groups of PVP. The adhesive forces of the PVP/PAA interpolymer complexes were higher than that of commercial Carbopol 971. Moreover, the adhesive force and the release rate can be controlled by changing the mole ratios of PVP and PAA. The release rates of ketoprofen from the PVP/PAA interpolymer complexes showed pH-dependency, and were slower at lower pH. The release rate of ketoprofen from the complex seemed to be mainly controlled by the dissolution rate of the complex above a pK(a) of PAA (4.75) and by the diffusion rate below the pK(a). The prepared complex appears to be an adequate carrier for the mucoadhesive drug delivery system.     

Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers.

Novel microgels composed of cross-linked copolymers of poly(acrylic acid) and Pluronics were evaluated as possible permeation enhancers for doxorubicin transport using Caco-2 cell monolayers as a gastrointestinal model. Pluronic, triblock copolymers of ethylene oxide (EO) and propylene oxide (PO), were chosen to represent the most hydrophobic (Pluronic L61 and L92 with average compositions of EO(3)PO(30)EO(3) and EO(8)PO(52)EO(8), respectively) and the relatively hydrophilic (Pluronic F127 with average formula EO(99)PO(67)EO(99)) extremes of this class of block copolymers. The weight ratio of Pluronic to poly(acrylic acid) in the microgels was set at 45:55. By inhibiting the P-glycoprotein (P-gp)-mediated doxorubicin efflux from the cells and enhancing the passive influx, the microgels were shown to enhance the overall cell absorption of doxorubicin. The enhancement effect was more pronounced than with a known penetration enhancer, Pluronic L61, and was comparable to that of Pluronic L92. Microgels exhibited synergism of the doxorubicin transport enhancement with Verapamil, a known inhibitor of the P-gp. The effects of the microgels were studied using the hydrophilic marker ([14C]mannitol) test and the MTT assay. Transepithelial electrical resistance (TEER) studies demonstrated that the microgels decreased TEER to about 80% of initial values, but these minor effects were fully reversible, indicating viability of the cells after incubation with microgels. No significant enhancement of [14C]mannitol transport by microgels was observed, relative to Carbopol 934NF (control polymer). Cytotoxicity studies confirmed that the transport-enhancing properties of the microgels were not due to damage of the Caco-2 cell monolayers.     

Preparation and in vitro characterization of poly(acrylic acid)-cysteine microparticles.

The purpose of the present study was to prepare and characterize a novel mucoadhesive microparticulate drug delivery system. Microparticles were prepared by the solvent evaporation emulsion technique using a poly(acrylic acid)-cysteine conjugate of an average molecular mass of 450 kDa with an amount of 308 micromol thiol groups per gram polymer. The cross-linking of thiol groups via the formation of disulfide bonds during this preparation process was pH-controlled. The resulting microparticles were characterized with regard to the degree of cross-linking and the amount of remaining free thiol groups, shape, size distribution and stability. Furthermore, the drug release behaviour using bromelain as model drug and the mucoadhesive properties were evaluated.Results demonstrated that the higher the pH of the aqueous phase was during the preparation process, the higher was the degree of cross-linking within the particles. However, even at pH 9, 8.9+/-2.2% of free thiol groups remained on the microparticles. Particles were of spherical and partially porous structure and had a main size in the range of 20-60 microm with a center at 35 microm. Because of the formation of disulfide bonds within the particles, they did not disintegrate under physiological conditions within 48 h. In addition, a controlled drug release of bromelain was achieved. Due to the immobilization of thiol groups on poly(acrylic acid), the mucoadhesive properties of the corresponding microparticles were improved threefold.These features should render poly(acrylic acid)-cysteine conjugate microparticles useful as drug delivery system providing a prolonged residence time on mucosal epithelia.     

Mechanically tough and highly stretchable poly(acrylic acid) hydrogel cross-linked by 2D graphene oxide

The mechanical performances of hydrogels are greatly influenced by the functionality of cross-linkers and their covalent and non-covalent interactions with the polymer chains. Conventional chemical cross-linkers fail to meet the demand of large toughness and high extensibility for their immediate applications as artificial tissues like ligaments, blood vessels, and cardiac muscles in human or animal bodies. Herein, we synthesized a new graphene oxide-based two-dimensional (2D) cross-linker (GOBC) and exploited the functionality of the cross-linker for the enhancement of toughness and stretchability of a poly(acrylic acid) (PAA) hydrogel. The 2D nanosheets of GO were modified in such a way that they could provide multifunctional sites for both physical and chemical bonding with the polymer chains. Carboxylic acid groups at the surfaces of the GO sheets were coupled with the acrylate functional groups for covalent cross-linking, while the other oxygen-containing functional groups are responsible for physical cross-linking with polymers. The GOBC had been successfully incorporated into the PAA hydrogel and the mechanical properties of the GOBC cross-linked PAA hydrogel (PAA-GOBC) were investigated at various compositions of cross-linker. Seven times enhancement in both toughness and elongation at break has been achieved without compromising on the modulus for the as-synthesized PAA-GOBC compared to the conventional N,N′-methylenebis(acrylamide) (MBA) cross-linked PAA hydrogel. This facile and efficient way of GO modification is expected to lead the development of a high-performance nanocomposite for cutting-edge applications in biomedical engineering.

Incorporation of a novel GO based cross-linker into the conventional poly(acrylic acid) hydrogel remarkably enhances the toughness and stretchability.     

Release of 5-amino salicylic acid from acrylic type polymeric prodrugs designed for colon-specific drug delivery.

New acrylic type polymeric systems having degradable ester or amide bonds linked to the bioactive agent 5-amino salicylic acid (5-ASA), were prepared and evaluated as materials for colon-specific drug delivery. Methacryloyloxyethyl 5-amino salicylate (MOES), and N-methacryloylaminoethyl 5-amino salicylamide (MAES) were prepared as the polymerizable derivatives of 5-ASA using activated ester methodology. The drug-containing monomers were free radically copolymerized with methacrylic acid or hydroxyethyl methacrylate, utilizing azobisisobutyronitrile as initiator. The polymer bearing 5-ASA units as side substituents of the acrylic backbone were obtained in the form of poly pendent esters or poly pendent amides. The drug release studies were performed by hydrolysis in buffered solutions (pH 1, 7.2, 8.5), or simulated intestinal fluid containing pancreatin to measure the chemical degradation expected to occur in the intestinal tract. The release profiles indicated that the hydrolytic behavior of polymers strongly depends on their degree of swelling, type of comonomer, and the nature of hydrolyzable bond. Implication of the results for use of these polymers for colon targeting are discussed.     

A spherical poly(acrylic acid) brush–enzyme block with high catalytic capacity for signal amplification in digital biological assays

Ultrasensitive determination of some ultra-low abundance biological molecules closely related to diseases is currently a wide concern and urgent issue to be addressed. Here, a spherical poly(acrylic acid)–alkaline phosphatase (SP–AKP) signal amplification block using spherical poly(acrylic acid) brush nanoparticles (SP) as the immobilized carriers was designed and synthesized optimally first. The results show that a single SP–AKP with high enzyme binding capacity and high catalytic ability (up to about 4800 effective free AKP per SP–AKP) has much greater fluorescence signal amplification ability than a single free AKP or SiO₂–COOH–AKP. Then, a droplet generation microfluidic chip was prepared successfully, and the SP–AKP was loaded and confined in a 14 pL droplet by adjusting its concentration to ensure at most one SP–AKP was encapsulated in each droplet according to Poisson''s theory. Finally, the fluorescence signals produced by 4-methylumbelliferyl phosphate (4-MUP) catalyzed via SP–AKP within 6 min were sufficient to be detected by a fluorescence microscope. Thus, the digital signal distribution of “1/0” (signal/background) was obtained, making this SP–AKP signal amplification block a promising enzyme label for potential high sensitivity digital biological detection applications.

A spherical poly(acrylic acid)–alkaline phosphatase (SP–AKP) fluorescent amplification block with a high catalytic capacity of about 100 times that of SiO₂–COOH–AKP, was proposed for ultrasensitivity digital biological detection.     

Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG-anhydride-drug linkages.

We have designed a new mucoadhesive drug delivery formulation based on H-bonded complexes of poly(acrylic acid) (PAA) or poly(methacrylic acid) (PMAA) with the poly(ethylene glycol) (PEG), of a (PEG)-drug conjugate. The PEGylated prodrugs are synthesized with degradable PEG-anhydride-drug bonds for eventual delivery of free drug from the formulation. In this work we have used indomethacin as the model drug which is PEGylated via anhydride bonds to the PEG. The complexes are designed first to dissociate as the formulation swells in contact with mucosal surfaces at pH 7.4, releasing PEG-indomethacin, which then hydrolyses to release free drug and free PEG. We found that as MW of PAA increases, the dissociation rate of the complex decreases, which results in decreased rate of release of the drug. On the other hand, the drug release from PEG-indomethacin alone and from solid mixture of PEG-indomethacin+PAA was much faster than that from the H-bonded complexes. Due to the differences in the thermal stability, PMAA complex exhibited slightly faster drug release than that of the PAA complex of comparable MW. These H-bonded complexes of degradable PEGylated drugs with bioadhesive polymers should be useful for mucosal drug delivery.     

An in vitro mucosal model predictive of bioadhesive agents in the oral cavity.

The formulation of a drug/carrier complex that can be distributed and retained for extended periods within the oral cavity would be advantageous in the treatment of local conditions. In this study, an in vitro system was developed to investigate the binding of bioadhesive macromolecules to buccal epithelial cells, without having to alter their physicochemical properties by the addition of 'marker' entities. In this innovative approach a lectin binding inhibition technique, involving an avidin-biotin complex and a colourmetric detection system, was used to evaluate polymer binding. 0.5% w/v polymer solutions in saline (pH 7.6) were left in contact with a standardized number of freshly collected human buccal cells for 15 min. The cells were then exposed to 10 mg L(-1) biotinylated lectin from Canavalia ensiformis followed by 5 mg L(-1) streptavidin peroxidase. The inhibition of lectin binding (i.e. by 'masking' of the binding site on the cell surface by the attached bioadhesive polymer) was measured and expressed as a percentage reduction in the rate of o-phenylenediamine oxidation over 1 min. From the wide range of polymer solutions screened, chitosan gave the greatest inhibition of lectin binding to the surface of buccal cells, while methylcellulose, gelatin, Carbopol 934P and polycarbophil also produced a substantial reduction. Lectin binding inhibition was also observed for a selected number of polymer solutions when screened at pH 6.2. The presence of bound chitosan, polycarbophil and Carbopol 934P on the buccal cell surface was confirmed using direct staining techniques. It was concluded that this assay can be used to detect polymer binding to the cells present on the buccal mucosa, and the information gained used in the development of retentive drug/polymer formulations.     

Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans.

The aim of the study was to develop a mucoadhesive ocular insert for the controlled delivery of ophthalmic drugs and to evaluate its efficacy in vivo. The inserts tested were based either on unmodified or thiolated poly(acrylic acid). Water uptake and swelling behavior of the inserts as well as the drug release rates of the model drugs fluorescein and two diclofenac salts with different solubility properties were evaluated in vitro. Fluorescein was used as fluorescent tracer to study the drug release from the insert in humans. The mean fluorescein concentration in the cornea/tearfilm compartment as a function of time was determined after application of aqueous eye drops and inserts composed of unmodified and of thiolated poly(acrylic acid). The acceptability of the inserts by the volunteers was also evaluated. Inserts based on thiolated poly(acrylic acid) were not soluble and had good cohesive properties. A controlled release was achieved for the incorporated model drugs. The in vivo study showed that inserts based on thiolated poly(acrylic acid) provide a fluorescein concentration on the eye surface for more than 8 h, whereas the fluorescein concentration rapidly decreased after application of aqueous eye drops or inserts based on unmodified poly(acrylic acid). Moreover, these inserts were well accepted by the volunteers. The present study indicates that ocular inserts based on thiolated poly(acrylic acid) are promising new solid devices for ocular drug delivery.     

Comparison of poly(acryl starch) and poly(lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine.

Drug delivery systems allowing controlled release of antigen are of particular interest in the development of vaccines. We have compared poly(acrylic starch) microspheres (PAS) and poly(lactide-co-glycolide) microspheres (PLG) as drug delivery systems for a rotavirus vaccine. The polymers are both biodegradable but have different degradation mechanisms and antigen release profiles. PAS are enzymatically degraded and have a continuous fast antigen release rate compared to the hydrolytically degraded PLG which release the incorporated antigen in a pulsatile manner. In this study mice were immunised intramuscularly and orally on three occasions with formalin-inactivated rotavirus (FRRV) incorporated in PAS and PLG and with FFRV alone. Serum and faeces samples were collected and analysed by ELISA for rotavirus specific IgG and IgA antibodies. A neutralising assay was also conducted on both serum and faeces antibodies. The two different polymer drug delivery systems induced different immune responses depending on administration route. PAS elicited significant antibody levels and neutralising effect after oral administration while PLG showed high antibody levels after intramuscular administration. The immune response appears to be dependent on the differences in antigen release and degradation mechanism for the two polymer systems.     

Biocompatibility of poly (DL-lactic acid/glycine) copolymers

In this review the authors discuss the polymer chemical, physical and cell biological aspects of poly (DL-lactic acid/glycine) copolymers, both in vitro and in vivo. The mechanism and rate of degradation and the degree of foreign body reaction were evaluated as a function of the molecular composition of the (co)polymer, its initial molecular weight and changes in crystallinity. Data from the literature concerning poly(lactic acid), poly(glycolic acid) and poly(amino acids) are included in this review. The choice to apply the polymers mentioned was determined by their nature: all are present in the human body as natural residues. Upon degradation, biocompatibility will thus not be impaired. The authors conclude that the degradation mechanism of poly(lactic acid), poly(glycolic acid) and poly(amino acids) are similar, i.e. bulk hydrolysis of ester bonds. The initial molecular weight and the chemical composition, determine the rate of degradation and the degree of foreign body reaction.     

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were less than 1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF). Gastric acid analysis and gastric biopsies were normal by light and electron microscopy. Gastric juice contained less than 3 pmol/ml of Cbl-binding ability due to IF (normal, 10-34 pmol/ml) and less than 2 pmol/ml of IF when measured with a radioimmunoassay (RIA) using normal human IF-[57Co]Cbl and rabbit anti-human IF serum (normal, 17-66 pmol/ml). However, RIA employing rabbit anti-hog IF serum gave values of 4-13 pmol/ml of IF (normal, 11-33 pmol/ml). This material had an apparent molecular weight of 40,000 (normal IF = 70,000). The IF from gastric biopsies appeared normal in terms of Cbl-binding ability, ileal binding, molecular weight, and both RIAs. This IF differed from normal mucosal IF, in that it lost its Cbl-binding ability when incubated at 37 degrees C at acid pH or in the presence of pepsin or trypsin. This loss was retarded when [57Co]Cbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P less than 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF). We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.     

Super tough poly(lactic acid) blends: a comprehensive review

Poly(lactic acid) or poly(lactide) (PLA) is a renewable, bio-based, and biodegradable aliphatic thermoplastic polyester that is considered a promising alternative to petrochemical-derived polymers in a wide range of commodity and engineering applications. However, PLA is inherently brittle, with less than 10% elongation at break and a relatively poor impact strength, which limit its use in some specific areas. Therefore, enhancing the toughness of PLA has been widely explored in academic and industrial fields over the last two decades. This work aims to summarize and organize the current development in super tough PLA fabricated via polymer blending. The miscibility and compatibility of PLA-based blends, and the methods and approaches for compatibilized PLA blends are briefly discussed. Recent advances in PLA modified with various polymers for improving the toughness of PLA are also summarized and elucidated systematically in this review. Various polymers used in toughening PLA are discussed and organized: elastomers, such as petroleum-based traditional polyurethanes (PUs), bio-based elastomers, and biodegradable polyester elastomers; glycidyl ester compatibilizers and their copolymers/elastomers, such as poly(ethylene-co-glycidyl methacrylate) (EGMA), poly(ethylene-n-butylene-acrylate-co-glycidyl methacrylate) (EBA-GMA); rubber; petroleum-based traditional plastics, such as PE and PP; and various biodegradable polymers, such as poly(butylene adipate-co-terephthalate) (PBAT), polycaprolactone (PCL), poly(butylene succinate) (PBS), and natural macromolecules, especially starch. The high tensile toughness and high impact strength of PLA-based blends are briefly outlined, while the super tough PLA-based blends with impact strength exceeding 50 kJ m⁻² are elucidated in detail. The toughening strategies and approaches of PLA based super tough blends are summarized and analyzed. The relationship of the properties of PLA-based blends and their morphological parameters, including particle size, interparticle distance, and phase morphologies, are presented.

PLA is a renewable, bio-based, and biodegradable aliphatic thermoplastic polyester that is considered a promising alternative to petrochemical-derived polymers in a wide range of commodity and engineering applications.     

Starch/Carbopol spray-dried mixtures as excipients for oral sustained drug delivery.

The present study evaluated if mixtures prepared by spray-drying an aqueous dispersion of Amioca starch and Carbopol 974P could be used as matrix for oral sustained drug delivery. The influence of the Amioca/Carbopol 974P ratio (0/100, 25/75, 50/50, 60/40, 85/15, 90/10, 95/5 and 100/0) and the pH and ionic strength (mu) of the dissolution medium on the drug release was investigated. The matrices composed of the spray-dried mixtures with 10% or 15% Carbopol 974P sustained the drug release over the longest time period. At this Carbopol concentration, shear viscosity measurements indicated the formation of an optimal network between the polymer chains of Amioca starch and Carbopol 974P, forming a rigid gel layer offering resistance to erosion during the dissolution experiments.     

Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins.

Sulfated polysaccharides (i.e., dextran sulfate) and sulfated polymers (i.e., sulfated polyvinylalcohol and sulfated copolymers of acrylic acid with vinylalcohol) were found to be potent and selective inhibitors of the replication of respiratory syncytial virus (RSV) and influenza virus type A (influenza A virus) but not of other myxoviruses (parainfluenza 3, measles, and influenza B viruses). The compounds were also inhibitory to human immunodeficiency virus type 1 (HIV-1) and HIV-2 and simian immunodeficiency virus but not simian AIDS-related virus. The mode of antiviral action of the sulfated polysaccharides and polymers can be attributed to an inhibition of virus binding to the cells (HIV-1), inhibition of virus-cell fusion (influenza A virus), or inhibition of both virus-cell binding and fusion (RSV). The fact that the sulfated polysaccharides and polymers are inhibitory to some myxoviruses and retroviruses but not to others seems to depend on the composition of the amino acid sequences of the viral envelope glycoproteins that are involved in virus-cell binding and fusion. All myxoviruses and retroviruses that are sensitive to the sulfated polysaccharides and polymers share a tripeptide segment (Phe-Leu-Gly). This tripeptide segment may be involved either directly (as a target sequence) or indirectly in the inhibitory effects of the compounds on virus-cell binding and fusion.     

Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly(acrylic acid) copolymers.

The capability of a family of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (Pluronic-PAA) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was studied. The unprotected lactone form of CPT, which possesses cytotoxic activity, is rapidly converted to the ring-opened carboxylate form under physiological conditions. Firstly, surfactant properties such as critical micellization concentration (CMC) of Pluronic-PAA copolymers were characterized. Then, the equilibrium solubility partitioning and hydrolysis of the lactone form of CPT in the presence of Pluronic-PAA in water and in human serum were analyzed. CPT solubility in polymer micellar solutions was ca. 3- to 4-fold higher than that in water at pH 5. The amount of CPT solubilized per PPO was considerably greater in the Pluronic-PAA solutions than in the parent Pluronic solution, which suggests that the drug is not only solubilized by the hydrophobic cores and also by the hydrophilic POE-PAA shells of the micelles. The equilibrium partition coefficient of the CPT lactone between Pluronic-PAA solutions and water exceeded (2-3) x 10(3). The complete solubilization of CPT and the absence of chemical interactions between CPT and Pluronic-PAA were confirmed by modulated temperature differential scanning calorimetry (MTDSC), infrared spectroscopy, and X-ray diffraction of films. The loading of CPT into the Pluronic-PAA micelles was able to prevent the hydrolysis of the lactone group of the drug for 2 h at pH 8 in water. When compared to the unprotected CPT, the kinetics of the CPT hydrolysis in human serum was about 10-fold slower in the Pluronic-PAA formulations.     

Synthesis of poly (N-isopropylacrylamide)-co-(acrylic acid) microgel-entrapped CdS quantum dots and their photocatalytic degradation of an organic dye

CdS quantum dots (CdSQDs) were generated inside the network structure of poly (N-isopropylacrylamide)-co-(acrylic acid) (pNIPAm-co-AAc) microgels and their ability to photocatalytically degrade organic dyes was evaluated using rhodamine B (RhB). The microgel-stabilized CdSQDs were generated by first enriching the microgels with Cd²⁺ followed by their reaction with Na₂S. The resultant microgels were characterized, and the CdSQDs were found to be distributed throughout the microgels. We went on to show that the hybrid microgels exhibited photocatalytic properties by exposing them to a solution of RhB followed by exposure to UV irradiation. We found that the hybrid microgels were able to degrade the RhB, while native microgels without CdSQDs present were not capable of the same behavior. Due to the thermo- and pH-responsivity of pNIPAm-co-AAc-based microgels their ability to degrade RhB was also evaluated as a function of environmental temperature and solution pH. We showed that the removal efficiency was highest when the microgels were in their swollen state, which we attribute to more effective mass transfer of the RhB inside the microgels when their porous structure is expanded. Finally, we show that the hybrid microgels can be reused multiple times, although their photocatalytic degradation ability decreases the more they are used, which may be a result of the aggregation and decomposition of the CdSQDs. We conclude that this approach is an effective means of removing RhB from water, which may be modified to photodegrade a variety of other organic compounds.

CdS quantum dots (CdSQDs) were generated inside the network structure of poly (N-isopropylacrylamide)-co-(acrylic acid) (pNIPAm-co-AAc) microgels and their ability to photocatalytically degrade organic dyes was evaluated using rhodamine B (RhB).