Recyclable characteristics of hyaluronate-polyhydroxyethyl acrylate blend hydrogel for controlled releases.

Hyaluronate-hydroxyethyl acrylate blend hydrogels which have a wide range of composition and characteristics were investigated. Glycidyl methacrylate derivatized hyaluronate (GMA-HA) were synthesized by coupling GMA to hyaluronate (HA) in the presence of a photoinduced initiator for polymerization. By copolymerizing radically GMA-HA and hydroxyethyl acrylate (HEA) under various compositions (weight ratios of HEA and GMA-HA: 1-20), GMA-HA hydrogels could be prepared in wide ranges of characteristics. These HA-PHEA gels possessed the feature that the dried ones recovered completely to the original swelling states on repeated runs, i.e. recyclable gels. The water contents of these hydrogels in equilibrium swellings in water (W(w)) were 0.99-0.86, and their viscoelastic properties were measured by a creep. The spontaneous elastic moduli were 1.05x10(5)-1.94x10(5) N m(-2), and they were mechanically tough. Their effective charge densities were estimated from the partition coefficients of sodium benzoate (NaBA) and decreased from -0.033 to -0.044 mol dm(-3) with increasing contents of HEA. Release of NaBA was studied, and the diffusion coefficients were found to be from 6.95x10(-10) to 0.12x10(-10) m(2) s(-1) with increasing the ratio of HEA. Their diffusion coefficients were found to be much less than the values estimated from the lattice model.

Preparation of a novel aggregate like sugar-ball micelle composed of poly(methylglutamate) and poly(ethyleneglycol) modified by lactose and its molecular recognition by lectin.

We report the preparation and characteristics of a novel micellar aggregate of an amphiphilic diblock copolymer, poly(methylglutamate) (PMG)-poly(ethyleneglycol) (PEG), whose terminus was modified by lactose lactone (LA). Due to the terminal LA moiety, this aggregate could be specifically recognized by RCA120 lectin. PMG-PEG-LA was synthesized by polymerizing the N-carboxy anhydride of L-glutamic acid gamma-methyl ester with H2N-PEG-LA as a polymerization initiator. By applying a fluorescence method using pyrene as a probe molecule, we found that PMG-PEG-LA could form the aggregate in aqueous solution. Fluorescence measurements showed that the critical aggregation concentration (C.A.C.) was 1.1 x 10(-5) M. The average diameter of the aggregate was 220 nm at 25 degrees C, as determined by the dynamic light scattering method. Circular dichroism measurements for the aggregate solution showed that the PMG residue took an alpha-helical structure, and that they associated to constitute the hydrophobic core of the aggregate. By adding RCA120 lectin to the aggregate solution, the turbidity of the solution increased rapidly, due to association of the aggregates. This implies that the aggregate could be recognized by lectin, and also suggests that sugar residues locate at the surface of the aggregates. From these findings, we concluded that the PMG-PEG-LA molecules form an aggregate like a "sugar ball" micelle, whose surface is covered by the sugar moieties. Application of the present aggregate system as a drug carrier is briefly discussed.

Characteristics of complexes composed of sodium hyaluronate and bovine serum albumin.

Complexes composed of sodium hyaluronate (NaHA) and bovine serum albumin (BSA) were studied to elucidate the exact composition of the complex, the phase separation, the electrophoretic mobility and the size using dynamic light scattering (DLS) and electrophoretic light scattering (ELS), etc. The phase diagram of the mixed solutions was determined. The complexes were soluble in neutral or weakly acidic pH regions and showed phase separation in the more acidic pH region. From the concentration of Na+ released from NaHA when it binds to BSA, the ratios of BSA to NaHA of the complexes were determined. In the region of soluble complexes, one BSA molecule was determined to bind with 15 carboxylic groups of NaHA and in the region of insoluble complexes to bind with 6 carboxylic groups. At the phase separation point, 117 BSA molecules bound with one NaHA molecule and 17% of the carboxylic groups of NaHA did not contribute to the binding of BSA. The sizes of the complexes decreased from several microm to several hundred nm as the binding ratio of BSA increases. Decreases in the viscosities of the mixed solutions were consistent with the decreases of the sizes. From these results, a model of complex formation is proposed.

Preparation and characterization of hyaluronate-hydroxyethyl acrylate blend hydrogel for controlled release device.

Hyaluronate-hydroxyethyl acrylate blend hydrogels were investigated as matrices for controlled release devices. Glycidyl methacrylate (GMA) derivatized HA (GMA-HA) was synthesized by coupling of GMA to HA in the presence of a suitable catalyst. These hydrogels were prepared by a free radical copolymerization of GMA-HA and hydroxyethyl acrylate. The water content of these hydrogels at equilibrium swelling in water (Ww) was 0.978+/-0.0073 (n=18); however, these hydrogel was mechanically tough and could be used as disk shape. The hydrogels swelling were found to depend on ionic strength and pH. The dried hydrogels quickly regained their original condition in water, and they swelled to more than 90% of its initial water contents after 30 min. This swelling-deswelling behavior was reproducible. The release of chlorpromazine HCl as a model cationic drug from the gels was suppressed significantly in water. The release increased with increasing the ionic strength and decreasing pH of bulk solutions.

Fluoride remineralization of demineralized bovine tooth enamel and hydroxyapatite pellets.

Both bovine enamel and hydroxyapatite pellets were remineralized in a fluoride-containing remineralization solution after prior demineralization for various lengths of time. In both the enamel and pellet systems, the degree of remineralization attainable was directly related to the extent of prior demineralization, although the demineralized material was never 100% recovered in remineralization. In some cases, fluoride levels up to several thousand parts per million were found at depths as great as 50 micrometers from the surface. The stoichiometry of the remineralized material and electron microprobe examination were consistent with the formation of fluoridated hydroxyapatite rather than calcium fluoride.

Novel topical fluoride delivery system I: remineralization of ground bovine teeth.

Laboratory studies were carried out on a newly conceived fluoride-containing remineralizing system with bovine teeth. The prototype fluoride delivery device involved micronized calcium fluoride maintained at the tooth surface with a cellulose film. Together with salivary calcium and phosphate (or simulated saliva), this system was able to generate and maintain the appropriate thermodynamic activity driving force for significant fluorapatite deposition in a reasonably short time (approximately 48 hr).

Novel topical fluoride delivery system II: remineralization of human teeth.

A recently conceived calcium fluoride-containing remineralization system was tested using human teeth in vitro. The influence of several variables (surface pretreatment, demineralization time, and remineralization time) was studied. Appreciable levels of fluoride taken up by pumiced human teeth were found at depths up to 50 micrometers when remineralization was carried out in either the remineralizing solution or saliva. The successful performance of the delivery device in these laboratory studies is encouraging and indicates that the logical evolution of the crude devices studied thus far could lead to clinically practical fluoride delivery devices.

In vivo remineralization using a sustained topical fluoride delivery system.

The efficacy of a new remineralization system was determined in vivo by maintaining a low concentration of approximately 1 ppm fluoride for 48 hrs against a demineralized human tooth. Human subjects were selected who wore removable partial dentures containing two or more of the demineralized teeth with film system. The findings indicate levels of fluoride uptake to 500 ppm at 50 micron depths in experimental sites.