Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema

BACKGROUND Tissue resident memory T(TRM)cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema.AIM To compare the efficacy and safety of the intralesional injection of 5-fluorouracil(5-FU)and triamcinolone(TA)with those associated with TA alone for the treatment of chronic eczema.METHODS A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only.Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes.All patients were followed up monthly for up to 1 year.RESULTS No serious adverse event was observed in either group.Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment,the relapse rate was significantly lower in the 5-FU+TA group than in the TA group.Histological examination showed significantly fewer CD8^(+)and CD103^(+)T cells but not CD4^(+)T cells in the 5-FU+TA group.CONCLUSION One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of T_(RM) cells in the lesional skin and the relapse rate of chronic eczema.

Synthesis and characterization of HPMA copolymer-5-FU conjugates

N-（2-Hydroxypropyl） methacrylamide copolymer-5-fluorouracil （PHPMA-FU） conjugates were synthesized by a novel and simplified synthetic route, and characterized by UV, FTIR and HPLC analyses. The conjugated content of 5-fluorouracil （5-FU） was 3.41 ± 0.07 wt%. The stabilities of PHPMA-FU conjugates under different conditions were studied. The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.

Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy

Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.

良性气道狭窄的药物治疗

气道损伤时,伤口愈合过程异常是导致肥厚性瘢痕形成和气道管腔狭窄的原因,愈合过程可分为3个阶段：炎症期、增生期及成熟期.针对不同愈合阶段,所应用的预防和治疗瘢痕形成及气道狭窄的药物是不同的.具体包括：抗生素和类固醇、丝裂霉素、紫杉醇、5-氟尿嘧啶/氟羟强的松龙结合物、卤夫酮、抗反流药物、免疫抑制剂、生长因子等.本文综述了上述药物在细胞、动物及临床试验中治疗气道狭窄的作用、安全性及应用前景.