Vitamin D3-Loaded Nanoemulsions as a Potential Drug Delivery System for Autistic Children: Formulation Development, Safety, and Pharmacokinetic Studies

Abstract

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 AUC0–72 and Cmax with decreased Tmax 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 role and impact of abnormal vitamin levels in autism spectrum disorders

“…162 These data support the idea that VD3 supplementation is a useful strategy for preventing anxiety and cognitive loss. 163 Maternal VD insufficiency is a common issue in population studies and is linked to an increased risk of ASD in infants. VVD synthesis begins with UVB irradiation.…”

“…162 These data support the idea that VD3 supplementation is a useful strategy for preventing anxiety and cognitive loss. 163…”

Safety Profile of Vitamin D in Italy: An Analysis of Spontaneous Reports of Adverse Reactions Related to Drugs and Food Supplements

“…An important issue affecting the spontaneous reporting systems is underreporting, which increased during the pandemic for drugs and food supplements [77]. Moreover, the Phytovigilance system collects spontaneous reports of ARs related to the intake of dietary supplements, herbal preparations and galenic formulations [79], but we have found only one report for VitD galenic formulations which are especially prescribed to administer high doses of VitD to enhance VitD bioavailability and palatability [80]. Also, the analysis of the suspected ARs associated with dietary supplements containing VitD and other ingredients did not permit the establishment of if the reported effects were directly related to VitD, to another component or to the association.…”

A Comparison and Safety Evaluation of Micellar versus Standard Vitamin D3 Oral Supplementation in a Randomized, Double-Blind Human Pilot Study

“…Human studies investigating the influence of different supplemental forms on Vitamin D bioavailability are still sparse [ 23 ]. Limited clinical data are available on the pharmacokinetics of novel Vitamin D delivery vehicles [ 25 , 26 , 27 , 28 , 29 ] as well as on the impact of different dosing and treatment schedules on Vitamin D 3 absorption in humans [ 30 , 31 , 32 , 33 ]. In these studies, the oral bioavailability of Vitamin D 3 is generally evaluated through the major circulating metabolite, 25-hydroxyvitamin D (25(OH)D), which has a circulating half-life of 3 weeks [ 34 ] and thus serves as a stable biomarker of systemic Vitamin D status [ 35 , 36 ].…”