Design and in vitro/in vivo evaluation of chitosan-polyvinyl alcohol copolymer material cross-linked by dynamic borate ester covalent for pregabalin film-forming delivery system

Int J Biol Macromol. 2024 Nov;281(Pt 4):136433. doi: 10.1016/j.ijbiomac.2024.136433. Epub 2024 Oct 14.

Abstract

This research introduced a novel polymer synthesized by combining chitosan and modified polyvinyl alcohol, cross-linked with boric acid using dynamic covalent bonds. The polymer was developed to formulate a pregabalin Film-forming system (FFS) for treating postherpetic neuralgia via topical application, showcasing notable skin adhesion and drug delivery properites. The chitosan-boric acid-modified polyvinyl alcohol polymer was analyzed using NMR, FTIR. The exceptional features of the optimized FFS were evaluated through rheometer, Differential scanning calorimetry (Tg = 45.98 °C), contact angle (θ = 78.62°). The elongation (60.05 ± 3.67 %), cohesion (56.94 ± 4.65 MPa) and skin adhesion (58.12 ± 2.99 kPa) of chitosan-boric acid-modified polyvinyl alcohol were found to be 5.2, 6.8, and 8.3 times higher than those of the pure chitosan film, attributed to the double network structure formed by the cross-linked reversible dynamic covalent bond. The optimized pregabalin FFS exhibited increased in vitro (86.25 ± 1.87 μg/g) and in vivo (100.42 ± 7.44 μg/g) skin retention amounts compared to in vivo oral administration (28.43 ± 4.61 μg/g). In summary, the utilization of borate ester dynamic covalent bonds in developing chitosan-based film-forming polymer proved beneficial in improving skin adhesion and topical therapeutic effectiveness, thereby mitigating the risk of systemic side effects associated with oral administration.

Keywords: Boric; Chitosan; Film; Film-forming systems; Polyvinyl alcohol; Pregabalin.

MeSH terms

  • Animals
  • Borates* / chemistry
  • Chitosan* / analogs & derivatives
  • Chitosan* / chemistry
  • Cross-Linking Reagents / chemistry
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Esters / chemistry
  • Male
  • Polymers / chemistry
  • Polyvinyl Alcohol* / chemistry
  • Pregabalin* / chemistry
  • Pregabalin* / pharmacology
  • Rats

Substances

  • Chitosan
  • Polyvinyl Alcohol
  • Pregabalin
  • Borates
  • Esters
  • Drug Carriers
  • Cross-Linking Reagents
  • Polymers