Characterization of smart auto-degradative hydrogel matrix containing alginate lyase to enhance levofloxacin delivery against bacterial biofilms.
The aim of the present work is the characterization of smart auto-degradable microspheres composed of calcium alginate/high methoxylated pectin containing an alginate lyase (AL) from Sphingobacterium multivorum and levofloxacin. Microspheres were prepared by ionotropic gelation containing AL in its inactive form at pH 4.0. Incubation of microspheres in Tris-HCl and PBS buffers at pH 7.40 allowed to establish the effect of ion-chelating phosphate on matrix erodability and suggested an intrinsically activation of AL by turning the pH close to neutrality. Scanning electron and optical microscopies revealed the presence of holes and surface changes in AL containing microspheres. Furthermore, texturometric parameters, DSC profiles and swelling properties were showing strong changes in microspheres properties. Encapsulation of levofloxacin into microspheres containing AL showed 70% efficiency and 35% enhancement of antimicrobial activity against Pseudomonas aeruginosa biofilm. Levofloxacin release from microspheres was not changed at acidic pH, but was modified at neutral pH in presence of AL. Advantageously, only gel matrix debris were detectable after overnight incubation, indicating an autodegradative gel process activated by the pH. Absence of matrix cytotoxicity and a reduction of the levofloxacin toxicity after encapsulation were observed in mammalian CHO-K1 cell cultures. These properties make the system a potent and versatile tool for antibiotic oral delivery targeted to intestine, enhancing the drug bioavailability to eradicate bacterial biofilm and avoiding possible intestinal obstructions.
Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata (UNLP), Calle 47 y115, C.P. 1900 La Plata, Buenos Aires, Argentina.
German A
GA
Islan
CIDCA (Centro de Investigación y Desarrollo en Criotecnología de Alimentos, UNLP-CONICET-CCT La Plata), Facultad Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Calle 47 y 117, C.P. 1900 La Plata, Buenos Aires, Argentina.
Cecilia
C
Dini
Laboratorio de Citogenética y Mutagénesis, Instituto Multidisciplinario de Biología Celular (IMBICE, CONICET-CCT La Plata-CICPBA), C.C. 403, 1900 La Plata, Buenos Aires, Argentina.
Laura C
LC
Bartel
Laboratorio de Citogenética y Mutagénesis, Instituto Multidisciplinario de Biología Celular (IMBICE, CONICET-CCT La Plata-CICPBA), C.C. 403, 1900 La Plata, Buenos Aires, Argentina.
Alejandro D
AD
Bolzán
Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata (UNLP), Calle 47 y115, C.P. 1900 La Plata, Buenos Aires, Argentina. Electronic address: grcastro@gmail.com.
Guillermo R
GR
Castro
D000464:Alginates / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D018441:Biofilms / Q000187:drug effects*; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D064704:Levofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008863:Microspheres; D012995:Solubility
D000464:Alginates; D000900:Anti-Bacterial Agents; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D064704:Levofloxacin; D020723:Glucuronic Acid
Alginate; Alginate (PubChem CID: 91666324); Alginate lyase; Autodegradable biogels; Controlled release; Levofloxacin; Levofloxacin hydrochloride (PubChem CID: 9908810); Pectin; Pectin (PubChem CID: 441476); Propylene glycol (PubChem CID: 1030)