Pentapeptide modified ethosomes for enhanced skin retention and topical efficacy activity of indomethacin

Abstract

Challenges associated with topical analgesics and anti-inflammatory drugs include poor drug penetration and retention at the desired lesion site. Therefore, improving these challenges would help to reduce the toxic and side effects caused by drug absorption into the systemic circulation and improve the therapeutic efficacy of topical therapeutic drugs. Pentapeptide (KTTKS) is a signal peptide in skin tissue, it can be recognized and bound by signal recognition particles. In the current study, we successfully prepared novel indomethacin (IMC) loaded KTTKS-modified ethosomes (IMC-KTTKS-Es), and the physicochemical properties and topical efficacy were investigated. Results showed that the prepared IMC-KTTKS-Es displayed a particle size of about 244 nm, a negative charge, good deformability, and encapsulation efficiency (EE) exceeding 80% for IMC, with a sustained release pattern. In vitro percutaneous permeation studies revealed that the skin retention was increased after the drug was loaded in the IMC-KTTKS-Es. Confocal laser scanning microscopy also showed improved skin retention of IMC-KTTKS-Es. In addition, IMC-KTTKS-Es showed improved topical analgesic and anti-inflammatory activity with no potentially hazardous skin irritation. This study suggested that the IMC-KTTKS-Es might be an effective drug carrier for topical skin therapy with a good safety profile.

Unlocking the potential of cosmetic dermal delivery with ethosomes: A comprehensive review

“…77,78 In addition, they can carry a wide range of drugs, including hydrophilic and hydrophobic compounds, making them a versatile drug delivery system. 79,80 They have a high drug-loading capacity, which means that they can carry a large amount of drug per vesicle, that improves the overall efficacy of the treatment and reduces the number of applications needed. 81 Moreover, the ethanol present in ethosomes can help stabilize the vesicles and protect them from degradation.…”

Surface Modification of Lipid-Based Nanocarriers: A Potential Approach to Enhance Targeted Drug Delivery

“…Lysine-threonine-threonine-lysine-serine is a short signal peptide originated from collagen hydrolysis which interacts with the skin by binding to signal recognition particles present in skin tissue thus improving intradermal drug retention at the lesion site. Skin retention analysis showed that the retention of indomethacin in the skin was 4.51-folds with surface modified ethosomes compared to its plain gel …”

“…Skin retention analysis showed that the retention of indomethacin in the skin was 4.51-folds with surface modified ethosomes compared to its plain gel. 48 Surface modification can also facilitate synergistic treatment for the management of psoriasis. Guo et al synthesized glycyrrhetinic acid-D-α-tocopherol acid polyethylene glycol succinate (GA-TPGS) to stabilize psoriasis by preventing inflammation and damage by lipid peroxidation.…”

“…Skin retention analysis showed that the retention of indomethacin in the skin was 4.51-folds with surface modified ethosomes compared to its plain gel. 48 …”

Silk peptide-hyaluronic acid based nanogels for the enhancement of the topical administration of curcumin

“…To improve the transdermal penetration and the retention of drugs in the skin, various nanocarriers (such as solid lipid nanoparticles, ethosomes, and emulsions) have been developed to improve topical transdermal delivery ( Ilic et al, 2021 ; El-Hashemy, 2022 ; Niu et al, 2022 ). Among various types of nanocarriers, nanogels have attracted increasing attention due to their unique advantages, including great colloidal stability, tunable size, large surface area for biological coupling, and porous structure for loading large amounts of drugs ( Sivaram et al, 2015 ; Liu et al, 2021a ).…”