Lipid-based
drug and vaccine delivery systems
Liposomes are one of the most versatile
biochemical tools. They are microscopic,
spherical closed vesicles composed of one
or more lipid bilayer that form when phospholipids
are hydrated. Hydrophilic molecules can
be incorporated into the aqueous compartment
and lipophilic molecules can be encapsulated
in the lipid bilayers. Liposomes by themselves
are considered nonimmunogenic, biodegradable
and nontoxic. They have been utilized in
numerous biomedical applications including
gene therapy, for delivery of drugs and
vaccines, cancer imaging agents and cosmetics.
Liposomes have the capability to incorporate
selected bioactive biologicals and adjuvant
molecules and potentiate their efficacy
and minimize their toxicity. They do this
by beneficially altering the biodistribution
and pharmacokinetics of the molecule in
the body following its administra-tion through
various routes of delivery.
My
research program is centered on the design,
formulation, development and characterization
of drug and vaccine delivery systems; particularly
those based on liposomes. A special focus
on the site-specific targeting, controlled
release, drug resistance, pharmacokinetic,
pharmacodynamic, metabolism and toxicity
of free and liposome-encapsulated biological
active agents.
Research Interests
1.
Liposomal delivery of antisense oligonucleotides.
Effect on P-glycoprotein function in multidrug
resistant cells in vitro and in vivo studies.
Cationic liposome formulations are used
to promote the penetration of antisense
oligonucleotides into the cell membrane
and protect them from enzymatic degradation
(nucleases).
2. Liposomal delivery of antimicrobial agents
towards resistant bacterial pathogens: pulmonary
and systemic infections. Construction of
liposomes with high encapsulation efficiency,
favorable antimicrobial release profile
and enhanced bactericidal activity, to overcome
the problem of bacterial resistance caused
by low permeability of the bacterial cell
envelope and by production of antimicrobial-inactivating
enzymes.
3. Liposomal formulations of drugs and vaccine
for oral delivery. Liposomes are used to
protect the encapsulated agents from the
harsh gastrointestinal milieu (low pH, phospholipases,
and bile salts) and to enhance their absorption
to the systemic circulation and to increase
the efficacy of these agents while minimizing
their frequency of administration. Special
liposomal formulation will be prepared,
characterized and assayed for their efficacy
in vitro and in animal models.
Selected publications
M. R. Mozafari, A. Omri. Importance of Divalent Cations in Nanolipoplex Gene Delivery. Journal of Pharmaceutical Sciences. 2007 (in press).
C. Mugabe, M. Halwani, A. O. Azghani, R. M. Lafrenie, A. Omri. Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas aeruginosa.. Antimicrobial Agents and Chemotherapy. 2006; 50: 2016-2022 [Pubmed]
C.
Mugabe, A.O. Azghani, A. Omri. Preparation and characterization of dehydration-rehydration vesicles loaded with aminoglycoside and macrolide antibiotics.
International Journal of Pharmaceutics 2006; 307(2):244-50 .[Pubmed]
G. Rukholm, C. Mugabe,
AO. Azghani, A. Omri. Antibacterial Activity
of liposome gentamicin against Pseudomonas
aeruginosa. A time kill study. International
Journal of Antimicrobial Agents. 2006; 27: 247-252. [Pubmed]
M. R. Mozafari, J. Flanagan, L. Matia-Merino, A. Omri, Z. E. Suntres, H. Singh. Recent trends in the lipid-based nanoencapsulation of antioxidants and their role in foods. Journal of the Science of Food and Agriculture. 2006; 86: 2038–2045. [Pubmed]
C.
Mugabe, A.O. Azghani, A. Omri. Liposome-mediated
gentamicin delivery: development and activity
against resistant strains of Pseudomonas
aeruginosa isolated from cystic fibrosis
patients. Journal of Antimicrobial Chemotherapy
2005; 55(2):269-271.[Pubmed]
S.
Rossi, A.O. Azghani, A. Omri. Antimicrobial
efficacy of a new antibiotic-loaded poly
(hydroxybutyric-co-hydroxyvaleric acid)
controlled release system. Journal of Antimicrobial
Chemotherapy 2004 ;54(6):1013-8.
[Pubmed]
M.
Anderson, A. Omri. The Effect of different
lipid components on the in vitro stability
and release kinetics of liposome formulations.
Drug Delivery 2004; 11(1):33-9.
[Pubmed]
M.
Anderson, C. Paradis, A. Omri. Disposition
of 3H-cholesteryl ether labeled
liposomes following intravenous administra-tion
to mice: comparison with an encapsulated
14C-inulin as an aqueous phase
marker. Drug Delivery. 2003; 10 (3): 193-200.[Pubmed]
A. Omri, Agnew BJ, Patel GB. Short-term
repeated dose toxicity profile of archaeosomes
administered to mice via intravenous and
oral routes. International Journal of Toxicology
2003; 22 (1): 9 – 23.[Pubmed]
G.B. Patel, A. Omri, L. Deschatelets, G.
D. Sprott. Safety of archaeosomes adjuvants
evaluated in a mouse model. Journal of Liposome
research. 2002; 12 (4): 353-372.
[Pubmed]
A. Omri, Suntres ZE, Shek PN. Enhanced Activity
of Liposomal Polymyxin B against Pseudomonas
aeruginosa in a Rat Model of Lung Infection.
Biochemical Pharmacology. 2002; 64 (9):
1407-1413.
[Pubmed]
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