Background::
All-trans retinoic acid (ATRA) is widely employed in the treatment of
various proliferative and inflammatory diseases. However, its therapeutic efficacy is imperiled
due to its poor solubility and stability. Latter was surmounted by its incorporation into a solid
matrix of lipidic nanoparticles (SLNs).
Methods::
ATRA loaded SLNs (ATRA-SLNs) were prepared using a novel microemulsification
technique (USPTO 9907758) and an optimal composition and were characterized in terms of
morphology, differential scanning calorimetry (DSC), and powder X-ray diffraction studies
(PXRD). In vitro release, oral plasma pharmacokinetics (in rats) and stability studies were also
done.
Results::
Rod-shaped ATRA-SLNs could successfully incorporate 3.7 mg/mL of ATRA, increasing
its solubility (from 4.7 μg/mL) by 787 times, having an average particle size of
131.30 ± 5.0 nm and polydispersibility of 0.283. PXRD, DSC, and FTIR studies confirmed the
formation of SLNs. Assay/total drug content and entrapment efficiency of ATRA-SLNs was
92.50 ± 2.10% and 84.60 ± 3.20% (n=6), respectively, which was maintained even on storage
for one year under refrigerated conditions as an aqueous dispersion. In vitro release in 0.01 M
phosphate buffer (pH 7.4) with 3% tween 80 was extended 12 times from 2h for free ATRA to
24 h for ATRA-SLNs depicting Korsmeyer Peppas release. Oral administration in rats showed
35.03 times enhanced bioavailability for ATRA-SLNs.
Conclusion::
Present work reports preparation and evaluation of bioenhanced ATRA-SLNs containing
a high concentration of ATRA (>15 times than that reported by others). Latter is attributed
to the novel preparation process and intelligent selection of components.
Lay Summary:
All-trans retinoic acid (ATRA) shows an array of pharmacological activities
but its efficacy is limited due to poor solubility, stability and side effects. In present study its
solubility and efficacy is improved by 787 and 35.5 times, respectively upon incorporation into
solid lipid nanoparticles (ATRA-SLNs). Latter extended its release by 12 times and provided
stability for at least a year under refrigeration. A controlled and sustained release will reduce
dose related side effects. ATRA-SLNs reported presently can thus be used in treatment
/prophylaxis of disorders like cancers, tuberculosis, age related macular degeneration and acne
and as an immune-booster.
Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles