Characterization and biocompatibility of organogels based on L-alanine for parenteral drug delivery implants.
The development of simple and efficient drug delivery systems for the sustained release of peptides/proteins and low molecular weight hydrophilic molecules is an ongoing challenge. The purpose of this work was to prepare and characterize novel biodegradable in situ-forming implants obtained via the self-assembly of L-alanine derivatives in pharmaceutical oils. Six different amphiphilic organogelators based on L-alanine were synthesized. These derivatives could successfully gel various vegetable and synthetic oils approved for parenteral administration. Gelation was thermoreversible, and phase transition temperatures depended on gelator structure, concentration and solvent. Hydrogen bonds and van der Waals interactions were shown to be the main forces implicated in network formation. Selected formulations were then injected subcutaneously in rats for preliminary assessment of biocompatibility. Histopathological analysis of the surrounding tissues revealed mild, chronic inflammation and an overall good biocompatibility profile of the implants over the 8 wk evaluation period. This study demonstrates that in situ-forming organogels represent a potentially promising platform for sustained drug delivery.
Motulsky
Aude
A
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-Ville, Montréal, Canada QC H3C 3J7.
Lafleur
Michel
M
Couffin-Hoarau
Anne-Claude
AC
Hoarau
Didier
D
Boury
Frank
F
Benoit
Jean-Pierre
JP
Leroux
Jean-Christophe
JC
D000409:Alanine / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry*; D004337:Drug Carriers / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry; D004343:Drug Implants / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry*; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology*; D020100:Hydrogels / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry*; D007263:Infusions, Parenteral / Q000379:methods*; D008297:Male; D008422:Materials Testing; D009930:Organic Chemicals / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry; D044367:Phase Transition; D051381:Rats; D017208:Rats, Wistar
D001672:Biocompatible Materials; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels; D009930:Organic Chemicals; D000409:Alanine