Lan Mo,Guang-lei Zhao,Xiao-feng Li,Xing-long Xiao,Ning He,Hai-xia Xu,Yi-gang Yu
Design and synthesis of prodrugs is an effective strategy to develop new drugs. Puerarin is well-known for its pharmacological properties in the treatment of many cardiovascular and cerebrovascular related diseases. To cope with its poor liposolubility that limited practical applications, we successfully developed a new type of clean and efficient esterification medium for acylation modification of puerarin and studied the relative oral absorption, including pharmacokinetics , tissue distribution and metabolite after oral taking of puerarin acid esters in comparison with free puerarin in rats. In the 1-Ethyl-3-Methylimidazoliumacetate, puerarin had the good solubility, and the reaction showed great initial rate (46.71 mmol/(L*h)) and substrate conversion (63.91%). The results of oral absorption showed that the administration of long-chain fatty acid esters of puerarin, puerarin hexanoate and puerarin myristate , resulted in significantly higher levels of puerarin in the plasma and tissues, especially in the heart, cerebral cortex, hippocampus and corpus striatum. Overall, these findings collectively supported that puerarin acid esters administration led to greater circulating concentration of puerarin and had a reduced excretion rate, providing significant advantages and theoretical basis for their application in functional foods and pharmaceutical industries.
Tranexamic acid (TA) is widely used clinically as a skin whitening agent for treating melasma and hyperpigmentation. However, oral administration of TA is often associated with adverse effects. Topical application could mitigate these issues, but the hydrophilic nature of TA limits its topical use. To overcome this limitation, we explored the design of TA alkyl ester prodrugs to enhance skin absorption. Our study specifically focused on the butyl and octyl ester derivatives of TA. The results demonstrated that TA4 and TA8 significantly improved skin penetration and deposition, by approximately 2–3 times compared to unmodified TA. Furthermore, these derivatives were rapidly hydrolyzed to release the parent drug within less than 2 h in both skin homogenates and blood. Safety assessments indicated no significant skin irritation in mice and revealed low cytotoxicity in HaCaT cells when exposed to the TA ester derivatives. We also developed a hydrogel formulation incorporating the TA derivatives, using hydroxyethyl cellulose, propylene glycol, Tween 80, and chlorobutanol. This formulation exhibited good skin absorption, stability, and user experience, making it a promising candidate for topical application. To sum up, the alkyl esterification prodrug design provides a promising approach for enhancing the skin delivery of TA.
Chitin nanofibers were prepared from commercially available chitin powder via esterification modification and subsequent ultrasound treatment. The obtained chitin nanofibers were characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), 13 C CP-MAS (cross-polarization under magic-angle spinning) solid state nuclear magnetic resonance (NMR), elemental analysis, and X-ray diffraction (XRD). Results showed that the esterification of chitin with maleic anhydride significantly improved the ultrasound disintegration of chitin fibrils into nanofibers. With increasing power and time, the ultrasound treatment yielded smaller chitin nanofibers with narrower size distribution, and the diameter of the chitin nanofibers could reach ∼15 nm. The effect of the ultrasound treatment on degree of acetylation and degree of substitution of the chitin nanofibers was negligible. However, crystallinity of the chitin nanofibers increased with increase in power and time of the ultrasound treatment.
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