The PLGA nanoparticles for sustainable release of CGRP to ameliorate the inflammatory and vascular disorders in the lung of CGRP-deficient rats

Drug Deliv. 2021 Dec;28(1):865-872. doi: 10.1080/10717544.2021.1902021.

Abstract

The calcitonin gene-related peptide (CGRP) has been demonstrated relating to vascular and inflammatory regulations not only the nerve systems. As the anti-inflammation factor and the most potent vasodilator, the CGRP holds therapeutic potentials for the treatment of cardiovascular diseases which was, however, limited by its peptide nature and short half-life. With advantages in improving the stability, circulation time and protection from degradation, the nanoparticles were promising as delivery carriers for the peptide. Nevertheless, few nanoparticulate systems were developed to deliver the CGRP peptide for the modulation of vascular or inflammatory functions instead of neural regulation. In this study, the CGRP was encapsulated into the poly (lactic-co-glycolic acid) (PLGA) nanoparticle for sustained release of CGRP in vivo. The nanoparticles recovered the systemic level of CGRP and the vascular inflammatory factors in the CGRP+/- rats comparing to the administration of (Dulbecco's Phosphate Buffered Saline) DPBS or peptide only. With the decrease of vascular wall thickness and the attenuation of the T cell infiltration in the lung, the polymer based CGRP delivery system showed potentials to facilitate the therapeutic effects of the CGRP which may help for the development of CGRP-based therapy in vascular and inflammatory disorder related diseases.

Keywords: CGRP; PLGA delivery; inflammatory and vascular disorders; nanoparticles; sustainable release.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / administration & dosage
  • Calcitonin Gene-Related Peptide / deficiency*
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Inflammation / drug therapy
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Diseases / drug therapy

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Calcitonin Gene-Related Peptide

Grants and funding

This research was financially supported by the National Natural Science Foundation of China [31900994 and 81871293] and the Natural Science Foundation of Fujian Province [2020J01632].