Injectable nanoparticle-loaded hydrogel system for local delivery of sodium alendronate.
Systemic administration of bisphosphonates, e.g. sodium alendronate (Aln) is characterized by extremely low bioavailability and high toxicity. To omit aforementioned drawbacks an injectable system for the intra-bone delivery of Aln based on Aln-loaded nanoparticles (NPs-Aln) suspended in a hydrogel matrix (gellan gum, GG) was developed. Aln was encapsulated in poly(lactide-co-glycolide) (PLGA 85:15) by solid-oil-water emulsification. Drug release tests showed that within 25 days all the encapsulated drug was released from NPs-Aln and the release rate was highest at the beginning and decreased with time. In contrast, by suspending NPs-Aln in a GG matrix, the release rate was significantly lower and more constant in time. The GG-NPs-Aln system was engineered to be easily injectable and was able to reassemble its structure after extrusion as shown by rheological measurements. Invitro studies showed that the GG-NPs-Aln was cytocompatible with MG-63 osteoblast-like cells and it inhibited RANKL-mediated osteoclastic differentiation of RAW 264.7 cells. The injectability, the sustained local delivery of small doses of Aln and the biological activity render the GG-NPs-Aln system promising for the local treatment of osteoporosis and other bone tissue disorders.
AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biomaterials, al. A. Mickiewicza 30, 30-059 Krakow, Poland. Electronic address: uposadow@agh.edu.pl.
Urszula
U
Posadowska
Academy of Sciences of the Czech Republic, Institute of Physiology, Department of Biomaterials and Tissue Engineering, Videnska 1083, 14220 Prague 4-Krc, Czech Republic. Electronic address: parizek@biomed.cas.cz.
Martin
M
Parizek
Academy of Sciences of the Czech Republic, Institute of Physiology, Department of Biomaterials and Tissue Engineering, Videnska 1083, 14220 Prague 4-Krc, Czech Republic. Electronic address: filova@biomed.cas.cz.
Elena
E
Filova
Wageningen University, Laboratory of Physical Chemistry and Colloid Science, Dreijenplein 6, 6703HB, Wageningen, The Netherlands. Electronic address: gosia.wlodarczyk-biegun@wur.nl.
Malgorzata
M
Wlodarczyk-Biegun
Wageningen University, Laboratory of Physical Chemistry and Colloid Science, Dreijenplein 6, 6703HB, Wageningen, The Netherlands. Electronic address: marleen.kamperman@wur.nl.
Marleen
M
Kamperman
Academy of Sciences of the Czech Republic, Institute of Physiology, Department of Biomaterials and Tissue Engineering, Videnska 1083, 14220 Prague 4-Krc, Czech Republic. Electronic address: lucy@biomed.cas.cz.
Lucie
L
Bacakova
AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biomaterials, al. A. Mickiewicza 30, 30-059 Krakow, Poland. Electronic address: epamula@agh.edu.pl.
Elzbieta
E
Pamula
D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006801:Humans; D020100:Hydrogels; D007267:Injections; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D020100:Hydrogels; D011135:Polysaccharides, Bacterial; D053245:RANK Ligand; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C048288:gellan gum; D019386:Alendronate
Gellan gum; Injectability; Nanoparticles; Osteoporosis; PLGA; Sodium alendronate