Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 µg/cm²) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 µg/cm²) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 µg/cm²) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.

Bacterial infections are mainly managed by the administration of antibiotics, which are either cytotoxic or cytostatic to microbes. In some cases, it is inconvenient to treat infections caused by bacteria using the traditional oral route for antibiotic administration. This can be due to the limited oral bioavailability of antibiotics, their gastrointestinal tract (GIT) adverse effects, and the increased possibility of the appearance of resistant strains. In addition, the fact that many populations are needle-phobic restricts the switch from the oral to the parenteral route. Furthermore, poor drug permeation throughout the stratum corneum of topically applied antibiotics causes low systemic bioavailability. Therefore, microneedles (MNs) have emerged as viable medicinal devices for the delivery of antibiotics, either for local or systemic effects. MNs represent a minimally invasive, painless way of administration that can be self-administered by the patient without the need of medical professionals. This review has specifically focused on MNs as a promising approach for the delivery of antibiotics; it has discussed the different types of MNs, their advantages, and possible limitations for the delivery of antibiotics. Recent studies on the incorporation of antibiotics into various types of MNs, either for topical or transdermal delivery are highlighted, and finally, we present the conclusion and future perspectives.

Among the drug delivery systems, hydrogels and nanogels have shown a vital role because of their advantageous 3D crosslinked networks. They have the propensity to absorb water due to their hydrophilic groups, making them excellent superabsorbents that are water-insoluble. Nanogels are crosslinked nano-sized hydrogels (20–200 nm) with greater tissue permeation due to their smaller size. Hydrogels and nanogels demonstrate many advantages, including biocompatibility, hydrophilicity, controlled drug release, and smart drug delivery. They are regarded as an interesting approach for the controlled release of medications since they can encapsulate drug molecules in their water-swollen network. Recent advances in polymer chemistry and nanotechnology have resulted in several significant improvements in the field of hydrogels and nanogels as drug delivery systems. In this chapter, the properties of hydrogels and nanogels, as well as their classification, drug release mechanisms, and applications for drug delivery, will be discussed.

Background and purpose: Cellulite is caused by changes in the metabolism of the fatty tissue beneath the skin. Methylxanthines and retinoids are commonly added to the different anticellulite products. However, their topical permeation into the dermis is limited. Thus, the objective of this research is to formulate a nanoemulgel (NEG) containing a triple therapy of caffeine, aminophylline, and tretinoin as a topical anticellulite product to improve their skin permeation. Furthermore, the influence of microneedles (MNs) as skin pre-treatment on the permeation of the NEG was investigated. Experimental approach: Various nanoemulsion (NE) formulations were prepared using high-energy ultrasonication with different compositions and sonication amplitudes. Several characterisation tests were employed to select the optimum NE formulation. Then, the optimised NE formulation was incorporated with hyaluronic acid to prepare the NEG, which was, in turn, subjected to various evaluations. An ex vivo permeation study using human skin was performed for the NEG compared to a control preparation of plain gel. Additionally, a microneedling pen was applied as a skin pre-treatment at varying lengths prior to NEG application to examine its impact on the NEG’s permeation. Key results: The selected NEG has a homogenous and consistent texture with no coarse particles, a droplet size of 175.8 nm and polydispersity index (PDI) of 0.19, an optimum pH value of 5.28, high drug content of caffeine, aminophylline, and tretinoin (99.35, 98.48 and 98.05 %, respectively), high drug release values of approximately 100 % within 6 hours, appro-priate viscosity, minimum skin irritation, and adequate short-term stability. The ex vivo permeation study showed that caffeine, aminophylline, and tretinoin permeated more and deposited in the skin with higher percentages from the NEG than plain gel. This skin deposition within the dermis was increased by applying the microneedling pen at varying lengths of 0.5, 1, and 2 mm as a skin pre-treatment. Conclusion: This combined approach of NEG formulation containing a triple therapy of caffeine, aminophylline, and tretinoin, along with MNs application, has the potential to serve as a topical anticellulite product, reducing cellulite formation and improving skin appearance.