posted on 2024-01-10, 19:35authored byPrabhanjan
S. Giram, Ramakrishna Nimma, Anuradha Bulbule, Amit Singh Yadav, Mahadeo Gorain, Nalukurthi Naga Venkata Radharani, Gopal C. Kundu, Baijayantimala Garnaik
A poly(d,l-lactide-co-glycolide)
(PLGA) copolymer was synthesized using the ring-opening polymerization
of d,l-lactide and glycolide monomers in the presence
of zinc proline complex in bulk through the green route and was well
characterized using attenuated total reflectance–Fourier transform
infrared, 1H and 13C nuclear magnetic resonance,
gel permeation chromatography, differential scanning calorimetry,
X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight,
etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized
using the synthesized PLGA and was employed to fabricate nanoparticles
for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and
PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics.
PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity
as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled
nanoparticles were observed to be better in CT-26-inoculated solid
tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor
growth significantly more (log p < 0.001) than
the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore,
no body weight loss, hematological, and blood biochemical tests demonstrated
the nanocarriers’ nontoxic nature. This work presents the use
of safe PLGA and the demonstration of a proof-of-concept of biotin
surface attached PLGA nanoparticle-mediated active targeted Ir administration
to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed
better due to specific active tumor targeting and greater cellular
uptake due to biotin.