Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers

Abstract

Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials

“…Many researchers have reported superior properties of transethosomes over classical ethosomes. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] Different types of edge activators and penetration enhancers have been investigated to produce ethosomal systems with better characteristics. Transethosomes were reported to entrap drugs with molecular weights ranging from 130.077 Da to 200-325 kDa.…”

“…71 This penetration enhancer was incorporated in transethosomes for the delivery of hyaluronic acid and siRNAs. 21,22 The authors named these transethosomes SPACE ethosomal system. The in vitro human skin penetration of hyaluronic acid transethosomes was 7.8±1.1-fold higher than buffer solution, 5.9±2.5-fold higher than buffer-ethanol solution, and 3.2±0.6-fold higher than classical ethosomes.…”

“…The penetration enhancement from the SPACE-peptide transethosomes was dependent on the concentration of the SPACE peptide in the formula. 21 siRNA-loaded transethosomes were named SPACE peptide-decorated cationic ethosomes (DOTAP-SPACE ethosomal system). The formulation contained SPACEconjugated siRNA encapsulated in a carrier made up of a cationic lipid (DOTAP), cholesterol, SPACE-conjugated lipids (SPACE peptide -POPE) and free SPACE peptide; all were suspended in buffer-ethanol solution 45% v/v.…”

Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done “WT”

“…Addition of Φ m parameter shows that there is a maximum volume of particles that can be added before the system becomes too viscous. Some examples of complex formulations with high viscosity and drug concentration currently on the market include biodegradable polymer-liquid carrier Eligard (leuprolide acetate) (16), Hyalgan (intra-articular injections based on sodium hyaluronate); Gel-One (cross-linked hyaluronate); Supartz FX (highly purified hyaluronic acid) (17), IM injection of oily system Faslodex (fulvestrant used in metastatic breast cancer), Lupron Depot extended release, highly concentrated recombinant interleukin-1 receptor antagonist (Kineret, anakinra 150 mg/mL), and a fully biodegradable D,L-lactic-glycolic acids copolymer-based cylindrical implant Zoladex (goserelin acetate used in prostatic carcinoma, a pre-loaded 1.5-mm-diameter cylinder in a special single-use syringe with a 14-gauge siliconized needle (2.11-mm outer diameter) for subcutaneous delivery of implant, see Fig. 3).…”

Effects of Skin Penetration Enhancers in Topical Antiaging Products Containing α-HydroxyAcids and Hyaluronic Acid

“…Advances in transdermal drug delivery offer a less invasive way of drug administration (1). Fortunately, studies suggest that efficient topical delivery of HA depends on the penetration enhancement strategies (2). One aim of the present study was to find the appropriate enhancers for topical delivery of HA.…”