Cellulose acetate butyrate-pH/thermosensitive polymer microcapsules containing aminated poly(vinyl alcohol) microspheres for oral administration of DNA

Gheorghe Fundueanu, Marieta Constantin, Fabrizio Bortolotti, Rita Cortesi, Paolo Ascenzi, Enea Menegatti

Research output: Contribution to journalArticle

Abstract

The aim of this work is to safely transport bioadhesive microspheres loaded with DNA to intestine and to test their bioadhesive properties. Poly(vinyl alcohol) (PVA) microspheres were prepared by dispersion reticulation with glutaraldehyde and further aminated. These microspheres were firstly loaded with plasmid DNA by electrostatic interactions and then entrapped in cellulose acetate butyrate (CAB) microcapsules for gastric protection. The entrapped PVA microspheres do not have enough force by swelling to produce the rupture of CAB shell, therefore the resistance of microcapsules was weakened by incorporating different amount of the pH/thermosensitive polymer (SP) based on poly(N-isopropylacrylamide-co-methyl methacrylate-co-methacrylic acid) (NIPAAm-co-MM-co-MA). This polymer is insoluble in gastric juice at pH 1.2 and 37 °C, but quickly solubilized in intestinal fluids (pH 6.8 and pH 7.4). Therefore, DNA loaded PVA microspheres were not expelled in acidic media but were almost entirely discharged in small intestine or colon. The integrity of DNA after entrapment was tested by agarose gel electrophoresis indicating that no DNA degradation occurs during encapsulation. The percentage of adhered microspheres on the mucus surface of everted intestinal tissue was 65 ± 18% for aminated PVA microspheres without DNA and almost 50 ± 15% for those loaded with DNA. Non-aminated PVA microspheres display the lowest adhesive properties (33 ± 12%). In conclusion DNA loaded microspheres were progressively discharged in intestine. The integrity of DNA was not modified after entrapment and release, as proved by agarose gel electrophoresis. Both loaded and un-loaded aminated microspheres display good bioadhesive properties.

Original languageEnglish
Pages (from-to)11-20
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume66
Issue number1
DOIs
Publication statusPublished - Apr 2007

Keywords

  • Bioadhesive microspheres
  • DNA
  • Drug delivery systems
  • pH/thermosensitive polymers

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Cellulose acetate butyrate-pH/thermosensitive polymer microcapsules containing aminated poly(vinyl alcohol) microspheres for oral administration of DNA'. Together they form a unique fingerprint.

  • Cite this