Li Xing,Liang Kaili,Dong Yingying,Li Shen,Gao Zhengnan,Wang Qing
In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4. Graphical Abstract
Ying Li,Danqing Wang,Shan Lu,Lijuan Zeng,Yu Wang,Wenting Song,Jianping Liu
The purpose of the study was to improve transdermal delivery of pramipexole via nanocrystals and investigate the enhancement micro-mechanism. Pramipexole nanocrystals were prepared using wet media milling method and incorporated into carbomer gel. In vitro permeation studies through rabbit ear skin indicated that the cumulative permeation amount of pramipexole from nanocrystals in 24 h was 2.75 times more than that from coarse suspension. Investigations of selective follicular closing technique indicated that approximately 33.88% of the total permeation from nanocrystals was contributed to the follicular pathway, which was confirmed by scanning electron microscopy images. In vitro permeation and in vivo pharmacokinetic studies indicated that pramipexole from nanocrystal gel showed a higher permeation profile than that from coarse suspension gel. Overall, nanocrystals could improve transdermal delivery of pramipexole through transepidermal and transfollicular pathways by the nanosized particles.
Sonodynamic therapy (SDT) is a novel therapeutic modality that is effective for the noninvasive treatment of dermatological diseases. As a ubiquitous large class of sonosensitizers, however, porphyrins suffer from poor skin permeability and the inefficient generation of reactive oxygen species. Herein, different-sized porphyrinic metal–organic frameworks (MOFs), PCN-224 (90, 125, and 200 nm), were developed via the coordination of tetra-kis(4-carboxyphenyl) porphyrin (TCPP) and the metal zirconium to enhance the local delivery of porphyrins, and fluorescent sonosensitizers (methylene blue or rhodamine 6G) were further incorporated to improve the sonodynamic effect, as well as to visualize the delivery of PCN-224 and its cargo. The skin penetration of PCN-224 was found to be increased with the reduction of particle size, and all three-sized samples could overcome the barrier of stratum corneum, even achieving the dermis of the porcine skin. Both intercellular and follicular pathways were noticed for three-sized PCN-224, while the follicular one played a more significant role in the penetration of the smallest PCN-224. The intact nanoparticles were found in the skin. At the initial stage, the nanoparticle and its cargo penetrated the skin as an intact entity, while the encapsulated rhodamine 6G was slowly released to the microenvironment of the skin from the nanoparticle with the prolongation of application. The combination of PCN-224 and methylene blue could increase the acoustically triggered generation of 1O2, distinctly boosting the lethal effect against the cancerous cell. Collectively, the study revealed the feasibility of PCN-224 for topical use, suggested an innovative method to enhance the sonodynamic effect, and proposed a possible mechanism for skin drug delivery of MOFs.
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