Pharmacokinetic Study of Triptolide Nanocarrier in Transdermal Drug Delivery System—Combination of Experiment and Mathematical Modeling

Abstract

Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the “first pass effect” of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin–blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three−layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.

Olive Oil-Based Reverse Microemulsion for Stability and Topical Delivery of Methotrexate: In Vitro

“…As the water content increases in RM, the disordering of lipid layers increases, leading to an increase in motional freedom of the lipid hydrocarbon chain, the fluidity in the stratum corneum of the skin, and interaction with protein probably through hydrogen bonding and sulfonic group of the AOT . Also, the possibility of diffusion during permeation MTX cannot be ruled out because sizes of MTX-RM are smaller than the mammalian cell pore that facilitates diffusion through the pore of the stratum corneum and appendage (Figure d,f, respectively), which may be the main reason for drug permeation in the beginning. ,,− …”

“…A broadening of this endothermic transition seems to be due to encapsulation of AOT microemulsion into the intercellular regions of the skin and denaturalization of protein via interaction of an anionic headgroup of the AOT with skin components as observed, and it can be correlated with the confocal laser scanning micrograph (Figure d,f) and ATR/FT-IR spectra (Figure ) of MTX-RM treated Swiss albino mice skin. There is the interaction of RM with the skin components, enhancing the movement in intercellular lipid and protein domains of the treated skin and perturbing its architecture for permeation. − …”

“…The MTX-RM due to the negative charge headgroup of the AOT interact with cell membrane glycolipid and protein for permeation and can entrap and interact with endosomes or lysosomes present in the cell, leading to the release of MTX. − …”

Multistage Self-Assembled Nanomaterials for Cancer Immunotherapy

“…They can circulate long in the blood flow and are more likely to escape from excreting through the kidney and being captured by the reticuloendothelial system (RES) in the liver, lung, and spleen, resulting in enhanced tumor accumulation. Some reviews have discussed the pharmacokinetics of nanoparticles after systemic administration in detail [112][113][114][115][116][117]. However, conventional nanomedicines still encounter the problems of low delivery efficacy and unsatisfied therapeutic outcomes due to the various physiological barriers in the body [118].…”

Modification with Conventional Surfactants to Improve a Lipid-Based Ionic-Liquid-Associated Transcutaneous Anticancer Vaccine

“…Transcutaneous vaccination is a patient-friendly, effective, and target-specific alternative vaccination/immunization approach because skin contains numerous immunoresponsive antigen-presenting cells (APCs), which are highly efficacious for immunoresponsive diseases such as cancer, anemia, HIV, and diabetes [ 4 , 5 ]. However, the lipidic arrangement of the stratum corneum (SC) hinders the permeation of large and hydrophilic molecules (proteins, peptides, and nucleic acids), which must be transported using a hydrophobic, lipophilic, or oil-based nanocarrier [ 6 , 7 , 8 , 9 ]. Ionic liquids (ILs), which are liquid salts with a melting temperature below 100 °C, can be used as reagents, solvents, and antisolvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs); as solvents, cosolvents, and emulsifiers in drug formulations; as pharmaceuticals (API-ILs) aiming at liquid therapeutics; and in the development and/or improvement of drug-delivery-based systems [ 10 ].…”