title: Development and characterization of new enzymatic modified hybrid calcium carbonate microparticles to obtain nano-architectured surfaces for enhanced drug loading.
abstract: OBJECTIVE
  Biopolymer-CaCO3 hybrid microparticles exposed to hydrolytic enzymes can provide new surface tailorable architectures. Soluble Alginate Lyase hydrolyzed alginate chains exposed on microparticle surface are generating considerable matrix changes. The change of porosity and surface to volume ratio is expected to influence absorption of drugs, thereby affecting controlled release profiles. The developed hybrid system potentially shows interesting properties for lung drug administration.
  
  
  METHODS
  Hybrid microparticles were developed by colloidal co-precipitation of CaCO3 in presence of biopolymers: alginate (Alg) or Alg-High Methoxylated Pectin (HMP), followed by treatment with Alginate Lyase (AL). Surface architectures were observed by SEM. The increase in area to volume ratio was confirmed by BET isotherms. Also, enzymatic changes were elucidated by biophysical methods (EDAX, DSC, FTIR, XRD) and determination of the total carbohydrates content. Levofloxacin (a fluoroquinolone antibiotic) as model drug was incorporated by absorption. The drug release profile and the antimicrobial activity of the microparticles were tested against Pseudomonas aeruginosa.
  
  
  RESULTS
  After enzyme treatment, microspheres showed 4μm diameter and increased porosity. While CaCO3-Alg microspheres resulted in a rougher surface, CaCO3-Alg-HMP ones exhibited "nano-balloon" patterns on surface. Both AL-treated microparticles showed up to 3 and 7 times higher Levofloxacin encapsulation than no treated ones. Microparticles showed controlled drug release profiles and enhanced antimicrobial effect. The present work demonstrates a significant progress in the development of new carriers with potential application for lung infections treatment.
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y115, CP 1900 La Plata, Argentina.
authors.forename: G A
authors.initials: GA
authors.lastname: Islan
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y115, CP 1900 La Plata, Argentina.
authors.forename: M L
authors.initials: ML
authors.lastname: Cacicedo
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y115, CP 1900 La Plata, Argentina.
authors.forename: V E
authors.initials: VE
authors.lastname: Bosio
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, UNLP-CONICET-CCT La Plata), Department of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y115, CP 1900 La Plata, Argentina. Electronic address: grcastro@gmail.com.
authors.forename: G R
authors.initials: GR
authors.lastname: Castro
mesh_terms: D002119:Calcium Carbonate / Q000737:chemistry*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D064704:Levofloxacin / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D011133:Polysaccharide-Lyases / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D064704:Levofloxacin; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase; D002119:Calcium Carbonate
keywords: Alginate; Alginate Lyase; Calcium carbonate; Controlled release; Drug loading; Hybrid systems; Levofloxacin; Microparticles; Pectin