Marwa Hasanein Asfour

Lamotrigine (LTG) is a second-generation antiepileptic drug that belongs to Biopharmaceutics Classification System (BCS) class II. LTG has a low probability of crossing the BBB if administered orally. This study was designed to fabricate LTG cubosomal dispersion that is further loaded in a thermosensitive in situ gel to increase nasal residence time and enhance drug absorption across the nasal mucosal membrane. LTG-loaded cubosomes exhibited an entrapment efficiency ranging from 24.83% to 60.13%, a particle size ranging from 116.2 to 197.6 nm, and a zeta potential ≤-25.5 mV. The selected LTG-loaded cubosomal formulation was loaded in a thermosensitive in situ gel (cubogel) employing different concentrations of poloxamer 407. In vitro release study revealed sustained drug release from cubosomal and cubogel compared with free drug suspension. In vivo studies revealed enhanced antiepileptic efficacy of LTG cubogel and LTG cubosomes compared with free drug in rats with pilocarpine-induced epilepsy by stimulating the release of gamma-aminobutyric acid (GABA), total antioxidant capacity (TAC), and serotonin and by inhibiting the release of Ca²⁺, dopamine, acetylcholine (Ach), C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP). LTG cubogel exhibited superior activity over LTG cubosomes. These findings reveal that the developed cubosomal thermosensitive in situ gel can enhance the antiepileptic efficacy of LTG via the intranasal route.

The aim of the current study is the development of a vitamin D₃ (VD3)-loaded nanoemulsion (NE) formulation to improve VD3 oral bioavailability for management of vitamin D inadequacy in autistic children. Eight NE formulations were prepared by high-speed homogenization followed by ultrasonication. Four vegetable oils were employed along with two concentrations of Span 20 as the emulsifier. Glycerol, fructose, and mango flavor were included as viscosity modifier, sweetening, and flavoring agents, respectively. The prepared VD3-loaded NE formulations exhibited high drug content (> 98%), droplet size (DS) ranging from 61.15 to 129.8 nm with narrow size distribution, zeta potential values between − 9.83 and − 19.22 mV, and acceptable pH values (4.59–5.89). Storage stability showed that NE formulations underwent coalescence and phase separation during 6 months at room temperature, whereas at refrigerated conditions, formulations showed slight creaming. The optimum formulation (VD3-NE6) revealed a non-significant DS growth at refrigerated conditions and spherical morphology under transmission electron microscopy. VD3-NE6 did not produce any toxic effects to rats treated orally for 3 months, where normal blood picture and kidney and liver functions were observed compared to control rats. Also, serum calcium, oxidative stress, and apoptosis biomarkers remained within normal levels, indicating the safety of the optimum formulation. Furthermore, evaluation of VD3-NE6 oral bioavailability depicted a significant increase in AUC_0–72 and C_max with decreased T_max compared to plain VD3. The optimum formulation demonstrated improved stability, safety, and oral bioavailability indicating the potential for successful management of vitamin D deficiency in autistic children.

The present study aimed to improve the neuroprotective effect of chrysin (CHR) by combining two formulation techniques, phospholipid complexation and solid dispersion (SD). CHR-phospholipid complex (CHR-PLC) was prepared through solvent evaporation. The molar ratio CHR/PL (1:3), which exhibited the highest complexation efficiency, was selected for the preparation of CHR-PLC loaded SD (CHR-PLC-SD) with 2-hydroxypropyl β cyclodextrin (2-HPβCD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HPβCD (1:2, w/w) displayed the highest aqueous solubility of CHR (5.86 times more than that of plain CHR). CHR-SD was also prepared using 2-HPβCD for comparison. The in vitro dissolution of CHR-PLC-SD revealed an enhancement in the dissolution rate over CHR-PLC, CHR-SD, and plain CHR by six times. The optimum formulations and plain CHR were evaluated for their neuroprotective effect on brain aging induced by D-galactose in mice. The results demonstrated a behavioral activity elevation, an increase of AMPK, LKB1, and PGC1α brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-α, and NF-κβ brain contents when compared with those in the D-galactose control group. Thus, the developed formulations stimulated neurogenesis and mitochondrial biogenesis as well as suppressed neuroinflammation and neurodegeneration. The order of activity was as follows: CHR-PLC-SD4 > CHR-PLC (1:3) > CHR-SD > plain CHR. Graphical Abstract