Abstract
The application of nanotechnology to drug delivery systems for cancer therapy has
progressively received great attention. The most heavily investigated approach is the
development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such
as poly (lactic-
co
-glycolic acid) (PLGA). These NPs could be
further improved by surface modification utilizing a hydrophilic biodegradable polymer
such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver
drugs such as brucine (BRU), which has shown its potential in cancer therapy. The
objective of the current investigation was to develop and evaluate the passive targeting
of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of
drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations
including particle size, zeta potential, morphological evaluation, entrapment efficiency
and percentage yield; total serum protein adsorbed onto NP surfaces; and
in vitro
release of the loaded drug. Factorial design was employed
to attain optimal PLGA-loaded NPs. Finally, the
in vivo
anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs
obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm
with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV.
Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than
70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP.
In vitro
drug release was less than 99.1% at 168 h. Finally,
significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA
NP formulations compared to both BRU solution and naked NPs.