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Increasingly attention has been paid to the transdermal drug delivery systems with microneedles owing to their excellent compliance, high efficiency, and controllable drug release, therefore, become promising alternative with tremendous advantages for delivering specific drugs such as huperzine A (Hup A) for treatment of Alzheimer’s disease (AD) yet with low oral bioavailability. The purpose of the present study is to design, prepare, and evaluate a dissolving microneedle patch (DMNP) as a transdermal delivery system for the Hup A, investigating its in vitro drug release profiles and in vivo pharmacokinetics as well as pharmacodynamics treating of AD. Skin penetration experiments and intradermal dissolution tests showed that the blank DMNP could successfully penetrate the skin with an adequate depth and could be quickly dissolved within 5 min. In vitro transdermal release tests exhibited that more than 80% of the Hup A was accumulatively permeated from DMNP through the skin within three days, indicating a sustained release profile. In vivo pharmacokinetic analysis demonstrated that the DMNP group resulted in longer T max (twofold), longer t 1/2 (fivefold), lower C max (3:4), and larger AUC (0–∞) (twofold), compared with the oral group at the same dose of Hup A. Pharmacodynamic research showed a significant improvement in cognitive function in AD rats treated with DMNP-Hup A and Oral-Hup A, as compared to the model group without treatment. Those results demonstrated that this predesigned DMNP is a promising alternative to deliver Hup A transdermally for the treatment of AD.

Chitosan nanoparticles (CS-NPs) are under increasing investigation for the delivery of therapeutic proteins, such as vaccines, interferons, and biologics. A large number of studies have been taken on the characteristics of CS-NPs, and very few of these studies have focused on the microstructure of protein-loaded NPs. In this study, we prepared the CS-NPs by an ionic gelation method, and bovine serum albumin (BSA) was used as a model protein. Dynamic high pressure microfluidization (DHPM) was utilized to post-treat the nanoparticles so as to improve the uniformity, repeatability and controllability. The BSA-loaded NPs were then characterized for particle size, Zeta potential, morphology, encapsulation efficiency (EE), loading capacity (LC), and subsequent release kinetics. To improve the long-term stability of NPs, trehalose, glucose, sucrose, and mannitol were selected respectively to investigate the performance as a cryoprotectant. Furthermore, trehalose was used to obtain re-dispersible lyophilized NPs that can significantly reduce the dosage of cryoprotectants. Multiple spectroscopic techniques were used to characterize BSA-loaded NPs, in order to explain the release process of the NPs in vitro. The experimental results indicated that CS and Tripolyphosphate pentasodium (TPP) spontaneously formed the basic skeleton of the NPs through electrostatic interactions. BSA was incorporated in the basic skeleton, adsorbed on the surface of the NPs (some of which were inlaid on the NPs), without any change in structure and function. The release profiles of the NPs showed high consistency with the multispectral results.

Microneedles (MNs) as a novel transdermal drug delivery system have shown great potential for therapeutic and disease diagnosis applications by continually providing minimally invasive, portable, cost-effective, high bioavailability, and easy-to-use tools compared to traditional parenteral administrations. However, microneedle transdermal drug delivery is still in its infancy. Many research studies need further in-depth exploration, such as safety, structural characteristics, and drug loading performance evaluation. Finite element analysis (FEA) uses mathematical approximations to simulate real physical systems (geometry and load conditions). It can simplify complex engineering problems to guide the precise preparation and potential industrialization of microneedles, which has attracted extensive attention. This article introduces FEA research for microneedle transdermal drug delivery systems, focusing on microneedle design strategy, skin mechanics models, skin permeability, and the FEA research on drug delivery by MNs.