The prevalence of childhood
dyslipidemia increases and is considered as an important risk factor for the incidence of
cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the
body weight, the proposed study aims at preparing transdermal niosomal
gels of
simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized
niosomes with 0.31 μm number-weighted size displayed highest
simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after
transdermal administration of niosomal
gels to rats showed significant reduction in
cholesterol and
triglyceride levels while increasing plasma
high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in
simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug
suspension. Hence, this transdermal
simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric
antihyperlipidemic formulation.