Biomedical Engineering Reference
In-Depth Information
interactions with RIF), was explored. Its action is similar to RIF, but it has been
associated with uveitis when used with clarithromycin or fluconazole. Different
RFB liposomal formulations were developed and characterised and their
in vivo
profile was compared with free RFB following i.v. administration to mice (Gaspar
et al.
2008a, b
). Liposomal RFB rendered higher concentration in liver, spleen and
lungs 24 h post administration compared with free RFB. The concentration of RFB
in these organs was dependent on the rigidity of liposomal matrix. Liposomal
RFB matrix prepared with DPPC and DPPG was the most effective and was
selected for biological evaluation in a mouse model of disseminated tuberculosis.
Compared with mice treated with free RFB, mice treated with rigid liposomal RFB
exhibited lower bacterial loads in spleen (5.53 log
10
vs. 5.18 log
10
) and liver
(5.79 log
10
vs. 5.41 log
10
). In the lungs, the level of pathology was lower in mice
treated with liposomal RFB. These results suggest that liposomal RFB was a prom-
ising approach for the treatment of extrapulmonary tuberculosis in human immu-
nodeficiency virus co-infected patients.
Finally, attempting to increase the delivery to alveolar macrophages, targeted lipo-
somes were developed.
O
-steroyl amylopectin (
O
-SAP) is a recognizement signal for
the uptake of pegylated liposomes by lung macrophages (Deol and Khuller
1997
).
Biodistribution of lung-specific pegylated MLV (PC): chol, dicetylphosphate (DCP):
monosialogangliosides: distearylphosphatidylethanolamine-poly(ethylene glycol) 2000
(DSPE-PEG 2000) were studied in mice. Findings showed a pronounced increase from
5.1% with conventional liposomes to 31% with pegylated liposomes containing
O
-SAP
in lungs accumulation 30 min after administration. Moreover, pretreatment of both
healthy and infected animals with conventional liposomes (1 h before the administra-
tion of modified liposomes) saturated the RES and the uptake level in the lungs rose to
approximately 40% for the targeted pegylated liposomes, after 30 min. On the contrary,
these liposomes showed 30-50% reduced uptake and accumulation in liver and spleen.
Also, the biodistribution in the different organs was similar in both animal groups show-
ing 40% accumulation in lungs of normal and tuberculous mice.
Simmilarly targeted pegylated MLV (eggPC: chol: DCP: DSPE-PEG 2000,
2:1.5:0.2:0.2 M ratio, with
O
-SAP included at a ratio to eggPC of 1:3 (wt/wt)) were
loaded with INH or RIF and administered into mice infected with a low dose
(1.5 × 10
4
CFU/mouse) of
M. tuberculosis
twice a week for 6 weeks. Liposomal drugs
at and below therapeutic concentrations (INH 12 and 4 mg/kg, RIF 10 and 3 mg/kg
bw) were more effective than free drugs against tuberculosis, as evaluated on the basis
of CFUs detected, organomegaly and histopathology. Furthermore, liposomal drugs
had marginal hepatotoxicities as determined from the levels of total bilirubin and
hepatic enzymes in serum. The elimination of mycobacteria from the liver and spleen
was also higher with liposomal drugs than with free drugs (Deol et al.
1997
).
2.2.2
Pulmonary Administration
Pulmonary drug delivery is a non-invasive technique and offers a large surface
area for solute transport, fast drug uptake and improved drug bioavailability. It is,
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