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

ISLAN GA; BOSIO VE; CASTRO GR

Taipei, Taiwan

Conferencia; 5th International Conference on Industrial Bioprocesses; 2012

National Taiwan University of Science and Technology - National Taiwan University - National Cheng Kung University - National Chung Hsing University

Opportunistic pathogens such as Pseudomona aeruginosa have been found in the respiratory andintestinal tracts of cystic fibrosis patients that can be hardly eliminated by therapeutic proceduresusing only antibiotics. The reason of antibiotic treatment failure is the presence of dense mucusmainly composed of alginate produced by infectious strain making a strong viscous gel barrier. Inorder to overcome that problem the aim of the present work is to develop a new formulation based onbiopolymeric microspheres containing alginate lyase (AL, enzyme able to cleave the glycosidiclinkages of alginate) and ciprofloxacin (CIP, fluoroquinolone antibiotic) for sustainable oral deliveryin cystic fibrosis patients.Alginate (ALG), ALG coated with High Methoxyl Pectin (HMP) and ALG-HMP blend biopolymerswere loaded with Cip and gelled in water-organic solvents mixtures by ionic crosslinking.Encapsulation of Cip was ranged between 46 to 85% under different experimental conditions.Aqueous solution of 1,2 propylenglycol (50 % w/w) was the best solvent mixture with about 85 %CIP encapsulation in all the biopolymeric matrices tested. The Cip release from ALG-HMP matrixwas reduced in 55 and 15 % compared to ALG and ALG-coated HMP matrices respectively under thesame experimental conditions. The selected matrix, ALG-HMP, was able to encapsulate 90 % ofalginate lyase, showing 38 % enzyme activity after release from the microspheres under simulatedintestinal conditions. Also, presence of AL in the matrix reduced 30 % the CIP release from themicrospheres under the same experimental conditions but the enzyme was not inhbited by Cip. ALactivity was partially preserved in simulated gastric fluids showing 26 % of intial immobilizedenzyme activity enough amount of the biocatalyst to hydrolize the alginate mucus. The results foundin our work are suggesting the ALG-HMP matrix containing Cip and AL as a promising system forthe cystic fibrosis treatment.