Alginate Lyase and Ciprofloxacin co-immobilization on biopolymeric microspheres for Cystic Fibrosis treatment

G.A. ISLAN; V.E. BOSIO; GR CASTRO

Taipei

Congreso; 5th International Conference on Industrial Bioprocesses; 2012

National Taiwan University of Science and Technology

Opportunistic pathogens such as Pseudomona aeruginosa have been found in the respiratory and intestinal tracts of cystic fibrosis patients that can be hardly eliminated by therapeutic procedures using only antibiotics. The reason of antibiotic treatment failure is the presence of dense mucus covering organs surface mainly composed of alginate produced by infectious strains making a strong viscous gel barrier. In order to overcome that problem the aim of the present work is to develop a new formulation based on biopolymeric microspheres containing alginate lyase (AL, enzyme able to cleave the glycosidic linkages of alginate) and ciprofloxacin (Cip, a fluoroquinolone antibiotic) for sustainable oral delivery in cystic fibrosis patients. Alginate (ALG) gels coated with High Methoxyl Pectin (HMP) and ALG-HMP blend biopolymers were loaded with Cip and gelled in water-organic solvents mixtures by ionic crosslinking. Encapsulation of Cip was ranged between 46.0 to 85.0% under different experimental conditions. Fifty percent of aqueous solution of 1,2 propylenglycol was the best solvent mixture with about 85 % CIP encapsulation in all the biopolymeric matrices tested. The Cip release from ALG-HMP matrix was reduced in 55 and 15 % compared to ALG and ALG-coated HMP matrices respectively under the same experimental conditions. The selected matrix, ALG-HMP, was able to encapsulate 90.0 % of AL, showing 38.0 % enzyme activity after release from the microspheres under simulated intestinal conditions. Also, presence of AL in the matrix reduced 30.0 % the CIP release from the microspheres under the same experimental conditions but the enzyme was not inhibited by Cip. AL activity was partially preserved in simulated gastric fluids showing 26 % of initial immobilized enzyme activity enough amount of the biocatalyst to hydrolyze the alginate mucus. The results found in our work are suggesting the ALG-HMP matrix containing Cip and AL as a promising system for the cystic fibrosis treatment.