Biomedical Engineering Reference
In-Depth Information
free drug (Jain et al. 2006 ). Other administration routes such as i.v. rendered poor
RIF accumulation in torax, while intratracheally 128,585 and 885 lung/plasma
ratios for niosomes and free drug, respectively were achieved in rats. This repre-
sented a 145-fold increase in the accumulation of RIF-loaded niosomes in lungs as
compared to the free drug (Mullaicharam and Murthy 2004 ).
Sustained release formulations help guard against the acquisition of drug resis-
tance, as there is less chance for missed doses leading to suboptimal drug concentra-
tions in the blood (Kisich et al. 2007 ). Recently, the performance of a subcutaneous
(s.c.) depot was surveyed. A single administration of RIF, INH and PYZ loaded in
186-290 nm PLGA nanoparticles at RIF 12 mg/kg, INH 10 mg/kg and PYZ 25 mg/kg
bw, maintained plasma, lungs and spleen drugs concentrations for more than
1 month, while free drugs were cleared from circulation after 12-24 h. When
administered to mice i.v. infected with 1 × 10 5 bacilli of M. tuberculosis , there were
undetectable bacterial counts in the different organs (Pandey and Khuller 2004 ).
Biodistribution and Therapeutic Efficacy of Liposomes
Intravenous liposomes carrying aminoglycosides showed to be effective
antimycobacterial agents. Aminoglycosides are potent antibiotics with bactericidal
activity against Gram-negative and Gram-positive organisms as well as a series of
intracellular pathogens. Aminoglycosides have post-antibiotic effect, synergy with
b-lactam antibiotics, rapid concentration dependent bactericidal effect and low cost
as well as low frequency of resistance to them for the treatment of serious bacterial
infections (Begg and Barclay 1995 ; Lacy et al. 1998 ; Lortholary et al. 1995 ; Poole
2005 ; Zembower et al. 1998 ). However, they require parenteral administration and
their high dosage often results in serious toxicity including ototoxicity and nephro-
toxicity (Kumana and Yuen 1994 ; Nagai and Takano 2004 ). Therefore, administration
of aminoglycosides are only limited to patients with severe bacterial infections,
especially in immunocompromised patients with mycobacterial infections (Cometta
and Glauser 1996 ; Maertens and Boogaerts 1998 ; Schiffelers et al. 2001 ).
One of the limitations of liposomes-based aminoglycoside antibiotics is their
low encapsulation efficiency, which results in formulations with low drug-to lipid
ratio. This, in turn, should require high amount of liposomal formulations to
achieve desirable therapeutic dose, a feature that defeat the purpose (Mugabe et al.
2006 ). However, for nephrotoxic drugs such as aminoglycosides an advantage of
liposome entrapment is their decreased renal excretion. Free aminoglycosides are
usually rapidly cleared from the blood by glomerular filtration, exposing renal
tubules to potentially toxic concentrations. An additional advantage is that upon
liposomal encapsulation aminoglycosides can be delivered to macropages, and
used against intracellular microorganisms that invade these cells.
In the first work, amikasine (AMK) loaded in multilamellar vesicles (MLV) (egg
phosphatydilcholine, eggPC) i.v. administered at 40 mg/kg increased the delivery of
AMK to the liver and spleen and showed higher and more prolonged levels in serum
(up to 24 h after administration) than free AMK that showed a rapid decline in serum
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