Titre du document / Document title

Preparation and in vitro evaluation of primaquine-conjugated gum arabic microspheres

Auteur(s) / Author(s)

NISHI K. K. ⁽¹⁾ ; JAYAKRISHNAN A. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Polymer Chemistry Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Satelmond Palace Campus, Trivandrum 695 012, INDE

Résumé / Abstract

Gum arabic, a branched polysaccharide, was oxidized using periodate to generate reactive aldehyde groups on the biopolymer. Primaquine, an 8-aminoquinoline, was covalently coupled onto oxidized gum arabic via an imine bond and simultaneously fabricated into microspheres of less than 2 μm in size by heat denaturation in a reverse emulsion of 1:1 light paraffin oil and toluene stabilized by sorbitan sesquioleate as the surfactant. The covalent binding of primaquine to the polysaccharide using the clinically used water-soluble form of the drug primaquine phosphate was achieved in the presence of borate buffer of pH 11. Up to 35% of the drug could be bound to the polymer backbone depending on the concentration of the drug employed initially and the degree of oxidation of the polysaccharide. Interestingly, both the aliphatic and the hindered aromatic amino groups of primaquine were found to react with the aldehyde functions through Schiff base formation leading to cross-linking of the polysaccharide with the drug itself. In vitro release of the drug from microspheres into phosphate buffered saline (PBS, pH 7.4, 0.1 M) at 37 °C showed that the release of primaquine from the matrix was slow, although gradually increased with time. The maximum released was below 50% of the drug payload even after 10 days. Release into simulated gastric and intestinal fluids was faster compared to the release in PBS due to rapid hydrolysis of the Schiff's linkage in the gastric fluid. A possible reason for the poor hydrolytic susceptibility of the Schiff's linkage is suggested based on the unequal reactivity of the amino groups on primaquine and its relevance in possible therapeutic application of this polymer-drug conjugate discussed.

Revue / Journal Title

Biomacromolecules   ISSN 1525-7797 

Source / Source

2004, vol. 5, n^o4, pp. 1489-1495 [7 page(s) (article)] (30 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Chemical Society, Washington, DC, ETATS-UNIS  (2000) (Revue)

Mots-clés anglais / English Keywords

Parasiticide ; Oside polymer ; Experimental study ; Kinetics ; In vitro ; Gastric juice ; Release ; Crosslinking ; Oxidation ; Covalent bond ; Immobilization ; Preparation ; Spherical particle ; Microparticle ; Antimalarial ; Primaquine ; Drug carrier ; Control release polymer ; Crosslinked polymer ; Gum arabic ;

Mots-clés français / French Keywords

Antiparasitaire ; Oside polymère ; Etude expérimentale ; Cinétique ; In vitro ; Liquide gastrique ; Libération ; Réticulation ; Oxydation ; Liaison covalente ; Immobilisation ; Préparation ; Particule sphérique ; Microparticule ; Antipaludique ; Primaquine ; Vecteur médicament ; Polymère vecteur ; Polymère réticulé ; Gomme arabique ;

Mots-clés espagnols / Spanish Keywords

Antiparasitario ; Osido polímero ; Estudio experimental ; Cinética ; In vitro ; Jugo gástrico ; Liberación ; Reticulación ; Oxidación ; Enlace covalente ; Inmovilización ; Preparación ; Partícula esférica ; Micropartícula ; Antipalúdico ; Primaquina ; Vector medicamento ; Polímero vector ; Polímero reticulado ; Goma arábica ;

Localisation / Location

INIST-CNRS, Cote INIST : 27371, 35400011400471.0460