Background: Honey bee propolis is one of the natural products reported in various traditional
systems of medicines, including Ayurveda. Caffeic acid phenethyl ester (CAPE) is an active
constituent of propolis which is well known for its anticancer potential. The therapeutic effects of
CAPE are restricted owing to its less aqueous solubility and low bioavailability.
Objective: In this study CAPE loaded folic acid conjugated nanoparticle system (CLFPN) was investigated
to enhance solubility, achieve sustained drug release, and improved cytotoxicity of
Methods: Formulation development, characterization, and optimization were carried out by the design
of experiment approach. In vitro and in vivo cytotoxicity study was carried out for optimized
Results: Developed nanoparticles showed particle size and encapsulation efficiency of 170 ± 2-195
± 3 nm and 75.66 ± 1.52-78.80 ± 1.25%, respectively. Optimized formulation CLFPN showed sustained
drug release over a period of 42 h. GI50 concentration was decreased by 46.09% for formulation
compared to CAPE in MCF-7 cells, indicating the targeting effect of CLFPN. An improved in
vitro cytotoxic effect was reflected in the in vivo Daltons Ascites Lymphoma model by reducing tumor
Conclusion: The desired nanoparticle characteristic with improved in vivo and in vitro cytotoxicity
was shown by the developed formulation. Thus it can be further investigated for biomedical applications.