Biomedical Engineering Reference
In-Depth Information
drug and a 100% efficacy on chloroquine-resistant P. berghei infected mice upon
i.p. administration (Peeters et al. 1989a, b ). On the other hand, multiple s.c. admin-
istration of desferroxamine B, (DFO, an iron chelate) loaded in 300-500 nm lipo-
somes at 800 mg DFO/kg/day at days −1 and 0, reduced parasitemia and long-term
survival of mice infected with P. vinckei (Postma et al. 1998 ). Finally, artemether
loaded in MLV (EggPC:chol, 4:3 M ratio) caused 100% cure by clearing the
recrudescent parasitaemia of mice infected with the virulent rodent malaria para-
site P. chabaudi chabaudi upon i.p. administration (Chimanuka et al. 2002 ).
Recently, nanostructured lipid carriers (NLC) have been explored as antima-
larial drug depots. In a first approach, artemether loaded in 60 nm NLC made
of glyceryl dilaurate (solid lipid), Capmul ® MCM (liquid lipid), tween 80 and
Solutol HS 15 were i.p. administered at 0.15 g (equivalent to the marketed i.m.
formulation) to mice infected with P. berghei . Artemether NLC was responsible
for an increased survival as compared with the same dose of i.m. commercial
formulation (Joshi et al. 2008a ). In the second work, curcuminoids (hidrofobic,
thermolabile and chemically sensitive molecules) were loaded in NLC made of
trimyristin, tristerin and glyceryl monostearate as solid lipids and medium chain
triglyceride as liquid lipid. Curcuminoids NLC increased the survival period of
mice as compared to control and free curcuminoids treated groups after 3 i.p.
doses in 3 consecutive days. Increased bioavailability of drug in its native form
was due to sustained release from the lipid nanoparticles depository, which
prevented the fast metabolism of curcuminoids (Aditya et al. 2010b ).
iv. Increased bioavailability upon oral administration . Primaquine loaded in
Miglyol nanoemulsions increased the AUC by 1.3 folds and produced higher
drug levels in the liver as compared to free primaquine. Primaquine nanoemul-
sions also suppressed parasitemia (~93%) and extended survival of mice infected
with P. berghei at doses 25% lower than free drug (Singh and Vingkar 2008 ).
Artemether loaded in a self-microemulsifying drug delivery system (Mandawgade
et al. 2008 ) and solid microemulsions (Joshi et al. 2008b ) produced an improve-
ment in antimalarial activity after oral administration to mice infected with
P. berghei as compared to i.m. administration of commercial formulation.
v. Increased brain delivery. The transferring (Tf) receptor is highly polarized at
the blood-brain barrier and is localized only on the apical membrane of endothe-
lial cells. The evidence supports an iron transport model in which iron-loaded Tf
is taken up by receptor-mediated endocytosis at the luminal membrane of brain
capillaries. The iron then dissociates from Tf in endosomal compartments and is
transcytosed by unknown mechanisms, while the Tf is retroendocytosed (Roberts
et al. 1993 ). On these bases, Tf-conjugated SLN were investigated for their abil-
ity to deliver quinine dihydrochloride to the brain, for the management of cere-
bral malaria (Gupta et al. 2007 ). Quinine dihydrochloride was loaded in
(108-126 nm) Tf grafted to SLN (hydrogenated SoyPC, triolein, chol, DSPE).
Upon i.v. administration, conjugation of SLNs with Tf significantly enhanced
the brain uptake of quinine. A higher dose percentage of quinine was recovered
from the brain following administration of Tf-SLNs compared with
unconjugated SLNs or drug solution. However, not the presence of quinine in
brain parenchima neither the antimalarial activity was determined.
Search WWH ::




Custom Search