Biomedical Engineering Reference
In-Depth Information
The i.v. via has been barely explored. In a recent work for instance, RIF loaded
in 265 nm gelatin nanoparticles was administered at 10 mg/kg bw to Balb/c mice
infected with aerosolized 1 × 10 5 M. tuberculosis (Saraogi et al. 2010 ). After a
4-week treatment period, RIF-loaded gelatine nanoparticles depicted almost two
fold reduction in mycobacteria CFU in lungs and spleen when compared with
untreated animals. A significant reduction in the number of bacilli recovered both
from the lungs and spleen as compared with of free RIF given orally was also pro-
duced. The i.v. administration of RIF gelatin nanoparticles allowed to reduce 28
doses (oral RIF daily) to ten doses (i.v. administered every 3 days). Gelatin nano-
particles offer a number of benefits because of their biocompatibility, biodegrad-
ability, low antigenicity, low cost and ease of their use as parenteral formulations
(Coester et al. 2000 ; Kaur et al. 2008 ; Verma et al. 2005 ). Though similar results
were obtained with other drugs and carrier systems such as PLGA nanoparticles
(Pandey et al. 2003a, b ) liposomes (Gaspar et al. 2008a, b ) as well as with ligand-
appended synthetic polymer based nanoparticles (Sharma et al. 2004 ), the need for
large amounts of the polymer, biodegradability, cost restriction of the polymer, the
hazard of residual organic solvents and a lower drug stability are some of the criti-
cal factors that shift the choice of formulation towards biodegradable nanoparticles
such as gelatin nanoparticles.
Two additional works explored the performance of alternative drugs loaded in
different formulations. In the first of them, clofazimine (CLF), a riminophenazine
drug with activity against disseminated M. avium nanosuspensions were prepared.
CLF accumulate within macrophages, where mycobacteria multiply but possess
poor solubility, being unsuitable for i.v. administration in patients with drug malab-
sorption. It is doubtful whether oral administration can lead to intracellular
concentrations high enough to kill the bacteria; additionally showed toxic side
affects. Nanosuspensions (100-1,000 nm) of nanocrystalline CLF i.v. administered
to C57BL/6 mice infected with M. avium at 20 mg/kg bw (Peters et al. 2000 ),
resulted in CLF acummulation in spleen, liver and lung (81.4, 72.5 and 35.0 mg/kg
tissue, respectively) higher that the MIC. Nanocrystallyne CLF was as effective as
liposomal CLF in reducing bacterial loads in liver, spleen and lungs. Preparation of
drug in form of nanosuspensions was shown to be a more cost effective and techni-
cally simpler alternative, particularly for poorly soluble drugs, and to yield to a
physically more stable product than liposome dispersions. In the second one, MOX,
loaded in non biodegradable poly (butyl-2-cyanoacrylate) nanoparticles and i.v.
administered to mice infected with M. tuberculosis resulted in a significant decrease
in mycobacteria counts in lungs (Shipulo et al. 2008 ).
Two further works explored the intraperitoneal (i.p.) administration. In 2003, the
quinolone norfloxacin was bound (through an a(N-C) bond sensitive to lysosomal
proteases, allowing release in the lysosomes (Peters et al. 2000 )), to a dextran poly-
mer (a conjugate large enough to impair renal clearance) bound to mannose and
administered to mice infected with M. bovis . The number of CFUs in lungs was
decreased, whereas the free drug was ineffective (Roseeuw et al. 2003 ). More
recently, RIF loaded in niosomes i.p. administered to mice rendered greater accu-
mulation of RIF in thoracic lymph nodes (46.2% of the administered dose) than
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