In vivo Pharmacokinetic Comparison of Oral and Polymeric Nanoparticles Loaded in Transdermal Bilayer Dissolving Microneedles for Nimodipine delivery

Background: Subarachnoid hemorrhage (SAH) is a disease that requires extensive treatment with medication that targets the brain and minimizes systemic adverse effects, preferably with a single daily medication. Nimodipine [NID] offers these properties to be used for this purpose.
Objective: The goal of the study was to accomplish a comparison in the pharmacokinetic parameters of oral nimodipine suspension and transdermal Polymeric Nanoparticles loaded bilayer dissolving microneedles to improve lower oral bioavailability.
Methods: Nimodipine was previously formulated as polymeric nanoparticles (PNPs) characterized by a particle size of 81.78 ± 0.6 nm, a polydispersity index of 0.046 ± 0.01, and a zeta potential of -18.96 mV. These nanoparticles were incorporated into bilayer dissolving microneedle patches (bDMNs) utilizing a casting technique, employing a 10% w/v polyvinyl alcohol (PVA) polymer matrix and 5% glycerin. A total of twelve male white albino rabbits, each weighing approximately 1500 ± 175 g, were randomly allocated into two groups of six animals. One group received an oral dose of nimodipine suspension via oral gavage, while the other group was administered the nimodipine-loaded transdermal bDMNs applied to the skin. The plasma concentration of nimodipine was quantified using reversed-phase high-performance liquid chromatography (RP-HPLC), following the establishment of a spiked calibration curve with plasma samples with the internal standard cilnidipine.
Results: The results displayed mean value of time and concentration needed to achieve the maximum effect were (Cmax= 42.54 ±3.4 ng/ml, Tmax= 1 ±0.02 h) for oral and (Cmax=64.66 ±2.9 ng/ml, Tmax=0.5±0.01h) for bDMN, respectively approving that the optimized transdermal bDMN exhibited higher plasma concentration with Tmax lower than oral route, achieving (1.9) fold rise in the calculated relative bioavailability.
Conclusions: The transdermal bDMNs could offer a promising and effective method for NID delivery to improved lower oral bioavailability by enhancing the delivery through skin.