Transdermal transport can be challenging due to the difficulty in diffusing active substances through the outermost layer of the epidermis, as the primary function of the skin is to protect against the entry of exogenous compounds into the body. In addition, penetration of the epidermis for substances hydrophilic in nature and particles larger than 500 Da is highly limited due to the physiological properties and non-polar nature of its outermost layer, namely the stratum corneum. A solution to this problem can be the use of microneedles, which “bypass” the problematic epidermal layer by dispensing the active substance directly into the deeper layers of the skin. Microneedles can be obtained with various materials and come in different types. Of special interest are carriers based on biodegradable and biocompatible polymers, such as polysaccharides. Therefore, this paper reviews the latest literature on methods to obtain hyaluronic acid-based microneedles. It focuses on the current advancements in this field and consequently provides an opportunity to guide future research in this area.

The effectiveness of transdermal drug delivery is restricted by the barrier properties of the stratum corneum. Ethosomes, as vesicular carriers, offer a promising approach to enhance dermal bioavailability. This study aimed to optimize ethosome composition and preparation parameters to improve physicochemical stability and performance. The influence of alcohols (ethyl, n-butyl, n-propyl, isopropyl, tert-butyl), glycols (propylene glycol, ethylene glycol, 1,3-butanediol), and surfactants (Tween 80, Mirasoft^® SL L60) was systematically investigated. Stability was evaluated through zeta potential (ZP), polydispersity index (PDI), and hydrodynamic diameter (D_h). The effects of phospholipid concentration and homogenization were also assessed. SEM imaging confirmed the spherical morphology of vesicles. The optimal formulation comprised 30% (w/w) ethanol, 2.5% (w/w) phospholipid, 10% (w/w) ethylene glycol, and 1.25% (w/w) Tween 80. A comparable mixed-surfactant system (0.625% w/w; 60% Tween 80 and 40% Mirasoft^® SL L60) exhibited similar stability, indicating that glycolipid-based biosurfactants can reduce conventional surfactant requirements. Homogenization significantly enhanced colloidal stability, lowering PDI from 0.366 to 0.083 and D_h from 254 nm to 156 nm, evidencing decreased aggregation and improved size uniformity. Overall, formulation composition and processing conditions critically determine ethosome stability and transdermal delivery efficiency.

Recently, intensive research has been conducted on effective and simple systems for delivering active substances deep into the epidermis, e.g., for the treatment of skin inflammation. One possibility can be the use of soluble microneedles in which active compounds are encapsulated. This article describes the preparation of modern carriers, namely microneedles with encapsulated extracts of red beet or parsley leaves, that are rich in active substances with antioxidant and anti-inflammatory properties, specifically betanin and apigenin. The concentration of hyaluronic acid sodium salt, the method of preparing the solution, and the technique of the complete filling of molds were optimized. Plant extracts were obtained with sonication or maceration. In order to characterize the extracts obtained, several techniques were employed, such as UV–Vis, LC–MS, GC–MS, and FTIR-ATR. The analyses performed allowed for confirmation of the presence of selected active substances in the extracts. The most optimal solution of the microneedles’ precursor turned out to be the one with a concentration of 10 wt.% of sodium hyaluronate, prepared by stirring and sonication. The most efficient extraction method for each plant was chosen, and the extracts were introduced into a solution of hyaluronic acid sodium salt. The resulting soluble microneedle patches can be used as an alternative to the traditional methods of delivering anti-inflammatory and antioxidant substances of plant origin.

Betanin is a hydrophilic antioxidant with limited physicochemical stability, motivating the development of vesicular carriers to improve its retention and regulate release. This study employed a systematic, stepwise formulation-screening approach to develop and characterize cholesterol-containing ethosomes, including biosurfactant-modified formulations, for betanin encapsulation. The effects of preparation conditions, surfactant type and concentration, cholesterol content, and betanin loading on colloidal properties and storage stability were evaluated. Encapsulation efficiency, loading capacity, and in vitro release were also investigated. Formulations containing 2.5% (w/w) phospholipid, 30% (w/w) ethanol, 10% (w/w) ethylene glycol, 1% (w/w) cholesterol, and 0.625% (w/w) Tween 20 or Tween 20/Mirasoft^® SL L60 mixture, prepared by 3 min homogenization, showed the most favorable performance. Betanin incorporation altered vesicle organization, while encapsulation and release strongly depended on surfactant composition and betanin loading. The highest encapsulation efficiency was 87.87 ± 3.22%, whereas the maximum loading capacity was 0.0271 ± 0.0026%. Release was incomplete and composition-dependent, ranging from 5.67 to 34.49% after 90 min at pH 5.8. The limited release indicated formulation-dependent betanin retention, which may favor controlled delivery but could also restrict active-compound availability. As skin permeation and biological safety were not evaluated, the relevance of these findings for dermal delivery remains to be established. Weibull analysis adequately described the nonlinear release profiles. These findings demonstrate that biosurfactant-modified ethosomes are tunable lipid nanocarriers with composition-dependent encapsulation and in vitro release properties.