Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration.
Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1-34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3-4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.
School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK. p.gentile@sheffield.ac.uk.
Piergiorgio
P
Gentile
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin 10129, Italy. vijaympharm@gmail.com.|School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. vijaympharm@gmail.com.
Vijay Kumar
VK
Nandagiri
School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. riteshpabari@rcsi.ie.
Ritesh
R
Pabari
Division of Biology, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. jdaly@rcsi.ie.
Jacqueline
J
Daly
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin 10129, Italy. chiara.tondaturo@polito.it.
Chiara
C
Tonda-Turo
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin 10129, Italy. gianluca.ciardelli@polito.it.
Gianluca
G
Ciardelli
School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. zramtoola@rcsi.ie.
Zebunnissa
Z
Ramtoola
D001861:Bone Regeneration; D002113:Calcification, Physiologic / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D065546:Drug Liberation; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D054457:Tissue Scaffolds / Q000737:chemistry*
D010281:Parathyroid Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D048271:Chitosan
bone tissue; nanoparticles; parathyroid hormone; poly(lactide-co-glycolide); scaffolds