Title:Phospholipid/Bile Salt Based Novel Mixed Nanomicelles of Methotrexate Co-encapsulated with Sesamol: Preparation, Characterization, and Evaluation of Antiradical Effects In Vitro
Volume: 8
Issue: 1
Author(s): Jessy Shaji*Dhanila Varkey
Affiliation:
- Department of Pharmaceutics, Prin. K.M. Kundnani College of Pharmacy, Mumbai, Maharashtra,India
Keywords:
Antioxidant, methotrexate, mixed nanomicelles, phospholipid, rheumatoid arthritis, sesamol.
Abstract: Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune
disease characterized by inflammatory activity, irreversible structural damage, and
oxidative stress. Methotrexate (MTX) is widely used for RA management; however,
MTX administration is associated with a decrease in the level of endogenous antioxidants.
Co-administration of sesamol could combat oxidative stress alongside MTX regimen.
The intent of the present study was to prepare, characterize, and evaluate the in vitro
radical scavenging effects of novel mixed nanomicelles (NMs) of MTX co-encapsulated
with an efficient natural antioxidant like sesamol.
Methods: Novel MTX-sesamol loaded NMs (MTX-Ses-NMs) composed of phospholipid
and sodium deoxycholate (SDC) were prepared by film hydration method and the micelle
size, zeta potential, and entrapment efficiency (EE) was measured. Additionally, MTXSes-
NMs were characterized for morphology, small-angle neutron scattering (SANS),
structural features by Fourier Transform Infrared spectroscopy (FTIR), 1H nuclear magnetic
resonance (NMR), and X-ray diffraction (XRD) studies. The antiradical effects of
MTX-Ses-NMs were evaluated by nitric oxide (NO) radical inhibition, hydroxyl radical,
and superoxide anion radical scavenging assays.
Results: MTX-Ses-NMs were fabricated successfully and the micelle size and zeta potential
were found to be 123 ± 76 nm and -46.8 ± 16.4 mV, respectively. The encapsulation
efficiency of MTX and sesamol in MTX-Ses-NMs was found to be 89.62 ± 1.58% and
86.77 ± 1.27%, respectively. Morphology study by transmission electron microscopy
(TEM), and field emission gun scanning electron microscopy (FEG-SEM) corroborates
the formation of NMs. FTIR, 1H NMR, and XRD studies validate the encapsulation of
MTX and sesamol within the micelle core. Analysis of SANS data confirms the presence
of micelles and showed a decrease in the thickness of micelles after drug loading. Moreover,
in all the antiradical assays, MTX-Ses-NMs exhibited superior radical scavenging activity
as compared to free MTX.
Conclusion: The rationale of co-encapsulating sesamol with MTX was to augment the
antiradical effects of the developed NMs and we achieved the improved antiradical status
of NMs in vitro. The novel MTX-Ses-NMs might prove beneficial in reducing the toxic
effects of MTX-induced oxidative stress in vivo.
