title: Gelatin Nanoparticles with Enhanced Affinity for Calcium Phosphate.
abstract: Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate material to introduce specific motifs for selective targeting to specific organs, but gelatin nanoparticles have not yet been modified to increase their affinity to mineralized tissue. By means of conjugating bone-targeting alendronate to biocompatible gelatin nanoparticles, a simple method is developed for the preparation of gelatin nanoparticles which exhibit strong affinity to mineralized surfaces. It has been shown that the degree of alendronate functionalization can be tuned by controlling the glutaraldehyde crosslinking density, the molar ratio between alendronate and glutaraldehyde, as well as the pH of the conjugation reaction. Moreover, it has been shown that the affinity of gelatin nanoparticles to calcium phosphate increases considerably upon functionalization with alendronate. In summary, gelatin nanoparticles have been developed, which exhibit great potential for use in bone-specific drug delivery and regenerative medicine.
authors.affiliation: Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525, EX, Nijmegen, The Netherlands.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Farbod
authors.affiliation: Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525, EX, Nijmegen, The Netherlands.
authors.forename: Mani
authors.initials: M
authors.lastname: Diba
authors.affiliation: Department of Solid State NMR, Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zinkevich
authors.affiliation: Biophysical Chemistry Group, Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, D-04103, Leipzig, Germany.|Institute of Organic and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, D-40225, Düsseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Biomaterials, Max Planck Institute for Colloids and Interfaces, D-14424, Potsdam, Germany.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Harrington
authors.affiliation: Department of Solid State NMR, Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands.
authors.forename: Arno P M
authors.initials: AP
authors.lastname: Kentgens
authors.affiliation: Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525, EX, Nijmegen, The Netherlands.
authors.forename: Sander C G
authors.initials: SC
authors.lastname: Leeuwenburgh
mesh_terms: D019386:Alendronate / Q000737:chemistry; D001861:Bone Regeneration; D002113:Calcification, Physiologic / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D002130:Calcium Phosphates; D005780:Gelatin; C020243:calcium phosphate; D005976:Glutaral; D019386:Alendronate
keywords: bisphosphonates; bone-specific; conjugation; gelatin nanoparticles; targeted delivery