Localized drug delivery using crosslinked gelatin gels containing liposomes: factors influencing liposome stability and drug release.
We describe a drug-delivery vehicle that combines the sustained release properties of liposomes with the structural advantages of crosslinked gelatin gels that can be implanted directly or coated onto medical devices. Liposome inclusion in gelatin gels does not compromise thermal stability nor does it interfere with the resiliency of gels to tensile force. However, electron spin resonance analysis of sequestered DPPC liposomes revealed a slight depression (ca. 1.0 degrees C) of the gel-to-fluid phase transition relative to liposomes in suspension. The level of liposome release from gels was determined by liposome concentration, liposome size, and the presence of poly(ethylene oxide) chains in the gel matrix or in the liposome membrane. Both neutral and charged liposomes displayed relatively high affinities for poly(ethylene glycol)gelatin gels, with only 10-15% release of initially sequestered liposomes while liposomes in which poly(ethylene glycol) was included within the membrane were not as well retained (approximately 65% release). The in vitro efflux of ciprofloxacin from liposomal gels immersed in serum was nearly complete after 24 h compared to 38% release of liposomal chlorhexidine after 6 days. The serum-induced destabilization of liposomal ciprofloxacin depended on the accessibility of serum components to gels as partly immersed gels retained approximately 50% of their load of drug after 24 h. In vivo experiments using a catheterized rabbit model of urinary tract infection revealed the absence of viable Escherichia coli on coated catheter surfaces in seven out of nine cases while all untreated catheter surfaces examined (n = 7) were contaminated.
DiTizio
V
V
Institute of Biomedical Engineering, University of Toronto, Toronto, Canada.
Karlgard
C
C
Lilge
L
L
Khoury
A E
AE
Mittelman
M W
MW
DiCosmo
F
F
D015060:1,2-Dipalmitoylphosphatidylcholine; D000465:Algorithms; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002784:Cholesterol; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019245:Compressive Strength; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D020100:Hydrogels; D008051:Lipid Bilayers; D008081:Liposomes; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013718:Tensile Strength; D014867:Water / Q000032:analysis
D000890:Anti-Infective Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D008051:Lipid Bilayers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D002939:Ciprofloxacin; D002784:Cholesterol