Background: Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes
ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid
nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting
alternatives to improve TPT nanoencapsulation.
Objective: This study seeks to prepare complexes between the cationic TPT and the negatively charged
dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control.
Methods: The optimum ionic molar ratio in DS-TPT complexation was determined, and the selected
complex was characterized by FTIR and solid-state 13C NMR. TPT solubility in the free and complexed
forms was also assayed. TPT-PLN was then obtained via a microemulsion technique, and particle size,
zeta potential, encapsulation efficiency, drug loading and drug recovery were determined. Additionally,
the TPT stability and in vitro release were determined from PLN and compared with free TPT, TPT-DS
complex and TPT encapsulated in nanostructured lipid carriers (NLC) of similar composition.
Results: TPT-DS complexation was confirmed by FTIR and NMR. TPT solubility in the complex was
drastically decreased when compared to free TPT. TPT-PLN had high encapsulation efficiency (97%)
and drug loading capacity (5.5%). Additionally, TPT-PLN showed a mean diameter, polidispersivity
index e zeta potential of 140 nm, 0.2 and -22 mV, respectively. The TPT chemical stability and release
from PLN were observed to be superior when compared to NLC.
Conclusion: PLN has shown to be a more effective nanosystem for TPT nanoencapsulation because
TPT loading, stability and release were superior when compared to TPT-NLC.