Self-assembled nanoparticles present unique properties
that have potential applications in the development of a
successful drug delivery system. Doxorubicin (DOX) is an
important anti-neoplastic anthracycline chemotherapeutic drug
widely described. However, it suffers from serious dose-dependent
cardiotoxicity. D-Limonene is a major constituent of numerous
citrus oils that is considered a specific monoterpene against free
radicals producing antioxidant activity. Herein, we aimed to design
three types of self-assembled nanodelivery systems (nanoemulsion,
niosomes, and polylactide nanoparticles) for loading both DOX
and D-limonene to enhance the solubilization of D-limonene and
provide antioxidant activity with excellent anticancer activity. As
confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with
diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The
zeta potential values were above −30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of
DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the
case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a
sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release
model for all developed nanoparticles was the Peppas−Sahlin model, demonstrating DOX release through Fickian diffusion
phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of D-limonene. The cytotoxicity study of the
DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the
DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the
cardioprotective effect of D-limonene in combination with DOX.

Title

ACS omega

Publisher

American chemical society

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

4.132

Publication Type

Both (Printed and Online)

Volume

7

Year

2022

Pages

42096–42104