Doina Mihai

Preparation and characterization of Ca-alginate microspheres by a new emulsification method

Abstract The preparation and characterization of Ca-alginate microspheres obtained by a new procedure from alginic acid, treated with an excess of NaOH and subsequently with a very concentrated solution of CaCl 2 are described. The produced particles have a spherical shape with an average diameter of 350 μ m. The particles show a relative dense and homogeneous internal structure in comparison with previously reported alginate microcapsules (the bulk density being 0.47 g/cm 3 ), consequently the particle matrix is characterized by a high density of charged carboxylic groups. Particles produced with a contact time of 1 h showed a degree of crosslinking of 54%. Microspheres have a good stability, and despite of very low degree of swelling, they have a good solvents regain, and an excellent ionic binding capacity of cationic drugs. After preparation the beads were loaded by ionic complexation with an antitumor aromatic tetramidine. In addition, the in vitro release of drug has been studied.

Pullulan–cyclodextrin microspheres: A chromatographic approach for the evaluation of the drug–cyclodextrin interactions and the determination of the drug release profiles

Pullulan microspheres containing cyclodextrin (CyD) were obtained by chemical crosslinking with epichlorohydrin of an alkaline solution of pullulan (Pul) and alpha-, beta- or gamma-CyD. The amount of alpha-, beta- and gamma-CyD in microspheres was 120, 156, and 138 micromol/g, respectively, as determined from the percentage of iodine incorporated in the hydrophobic cavity of CyDs. Microspheres were packed in a glass column and the liquid chromatographic behaviour by isocratic elution of different drugs or typical organic compounds (TOC), taken as model drugs, was investigated. The increase of the retention volume (V(R)) of each compound, depending on the interaction(s) between CyDs cavity and the considered molecule, is characterized by a broadening of the peaks. The interaction coefficient K, corresponding to the ratio between the V(R) value of each tested molecule on Pul-alpha-, Pul-beta- and Pul-gamma-CyD active stationary phase and the V(R) value of benzoic acid on St/maltodextrin neutral stationary phase, was determined. According to K values, the accurate prediction can be done on the potential drugs to be conditioned in suitable CyD cavity. Values of K allow to anticipate the release profiles of drugs considered.

Chemical reactions on polysaccharides: I. Pullulan sulfation

Abstract In this paper, studies on the reaction parameters of sulfation of pullulan with SO3, used as a complex with organic bases are reported. The differences in reactivity of pullulan towards dextran sulfation were attributed both to the differences of structures of two polysaccharides and to the differences of their solubilities in the reaction media. The influence of the reaction conditions on the characteristics of the macromolecular chain was investigated.

Chemically modified exopolysaccharide pullulans: physico-chemical characteristics of ionic derivatives

Abstract The paper presents some physico-chemical characteristics of dilute solutions of exopolysaccharide pullulan and its carboxymethyl, sulfoethyl and sulfopropyl ionic derivatives. On-line size exclusion chromatography/multi-angle laser light scattering (SEC/ MALLS) was used for establishing their weight average molecular weight ( M w ), number average molecular weight ( M n ), polydispersity index ( I p = M w / M n ) and radius of gyration R g .

Curdlan microspheres. Synthesis, characterization and interaction with proteins (enzymes, vaccines).

Microparticles of curdlan, synthesized through crosslinking with epichlorohydrin in organic suspension media, were chemically modified with the aim of introducing strongly and/or weakly acidic anionic and palmitoyl hydrophobic groups. Microparticles of both curdlan and curdlan derivatives were physico-chemically characterized. Study of the interaction with enzymes, such as lysozyme, and vaccines, such as tetanus anatoxin, showed a co-operative protein retention effect, induced by electrostatic and hydrophobic forces. The results of the in vitro release studies on support-protein complexes recommend them as potential controlled release systems.

Chemical reaction on polysaccharides: V. Pullulan chloroalkylation

The article discusses the synthesis of pullulan derivatives containing chloroalkyl groups by the reaction of crosslinked pullulan microparticles with different chloroalkyl chlorides in organic basic solvents. These new products may allow the attachment of various bioactive compounds by covalent bonding.

New Polysaccharide-based Microparticles Crosslinked with Siloxane: Interactions with Biologically Active Substances

The interaction of microparticles of carboxymethyl pullulan crosslinked with siloxane (provided by a new crosslinking agent: 3-(glycid oxypropyl) trimethoxysilane) with biologically active molecules, such as enzymes (lysozyme) and drugs (propranolol, quinidine) was studied. The anionic amphiphilic supports retained through electrostatic and/or hydrophobic forces, variable amounts of the substances as a function of their structure, such as crosslinking degree and amount of uncrosslinked alkylsilane chains. The absorption of lysozyme on the supports followed the Langmuir isotherm, which allowed the calculation of constants k1 and k2. Both retention and in vitro release behavior of these support potential applications in controlled drug release as well as immobilization and purification of enzymes.

Chemical reactions on polysaccharides. VII. Sulfonamide derivatives of dextran

The amidation reaction of linear and crosslinked sulfopropyl dextran with protic and dipolar aprotic amidic solvents such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide and hexamethylphosphoramide, at mild temperature, was studied. The composition of the final products can be adjusted by molar ratios of reagents, temperature and duration of reaction. The final products are water-soluble or highly water-swellable hydrogels which possess an ion-exchange ability due to their content of unreacted sulfonic acid groups. Some physico-chemical characteristics of these new polymers are pointed out.

Macromolecular-Drug Conjugates—Nalidixic Acid and Oxacillin-Dextran

Dextran conjugates with nalidixic acid and oxacillin, were prepared in two ways: (a) by the reaction of the drugs with chloroacetylated crosslinked dextran microparticles and (b) by the reaction of the drugs with crosslinked polysaccharide microparticles in the presence of a coupling agent. The in vitro behavior of these conjugates was studied and the mechanism of drug release was determined.