Multiple drug delivery hydrogel system for spinal cord injury repair strategies.
The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug delivery systems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drug delivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion.
Department of Chemistry, Materials and Chemical Engineering Giulio Natta, Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy.
Giuseppe
G
Perale
Filippo
F
Rossi
Marco
M
Santoro
Marco
M
Peviani
Simonetta
S
Papa
Dorina
D
Llupi
Paola
P
Torriani
Edoardo
E
Micotti
Sara
S
Previdi
Luigi
L
Cervo
Erik
E
Sundström
Aldo R
AR
Boccaccini
Maurizio
M
Masi
Gianluigi
G
Forloni
Pietro
P
Veglianese
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004058:Diffusion; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004359:Drug Therapy, Combination; D020100:Hydrogels / Q000737:chemistry*; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012995:Solubility; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D013499:Surface Properties; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D018696:Neuroprotective Agents