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...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.展开更多
Biphasic drug release is a popular advanced drug controlled release profle that has been drawing increasing attention from many felds.Electrospun nanofbers and their derivatives can be act as a strong platform for dev...Biphasic drug release is a popular advanced drug controlled release profle that has been drawing increasing attention from many felds.Electrospun nanofbers and their derivatives can be act as a strong platform for developing biphasic release dosage forms.In this study,a modifed coaxial electrospinning was implemented,in which little molecule solutions that contain a drug ibuprofen(IBU)and polyethylene glycol(PEG)were exploited as a sheath fuid to surround the core solutions composed of polymer ethyl cellulose(EC)and IBU.The prepared nanofber-based structural hybrids,i.e.,engineered spindles-on-astring(SOS)products,were successfully created and subjected to a series of characterizations.Scanning electron microscopy and transmission electron microscopy results showed the engineered SOS structures.IBU and the carriers EC and PEG had good compatibility,as suggested by X-ray difraction and Fourier transform infrared spectroscopy assessments.In vitro dissolution tests verifed that the SOS products were able to provide a typical biphasic release profle,releasing 40%of the loaded IBU within 1 h in an immediate manner in the frst phase,and the rest of the IBU in a sustained manner in the second phase.A combined mechanism of erosion and difusion is proposed for manipulating the IBU molecule release behaviors.展开更多
基金supported by the National Natural Science Foundation of China[grant No.81803466]the Research and Development Plan for Key Areas in Guangdong Province[grant No.2019B020204002]the National Science and Technology Major Program[grant No.2017zx09101001].
文摘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.
基金The study is fnancially supported by the Medical Engineering Cross Project between University of Shanghai for Science&Technology and Navy Military Medical University(No.2020201)the Natural Science Foundation of Shanghai(No.20ZR1439000)the National Natural Science Foundation of China(No.51803121),and Projects 2019-YH-15 and 21QNPY062.
文摘Biphasic drug release is a popular advanced drug controlled release profle that has been drawing increasing attention from many felds.Electrospun nanofbers and their derivatives can be act as a strong platform for developing biphasic release dosage forms.In this study,a modifed coaxial electrospinning was implemented,in which little molecule solutions that contain a drug ibuprofen(IBU)and polyethylene glycol(PEG)were exploited as a sheath fuid to surround the core solutions composed of polymer ethyl cellulose(EC)and IBU.The prepared nanofber-based structural hybrids,i.e.,engineered spindles-on-astring(SOS)products,were successfully created and subjected to a series of characterizations.Scanning electron microscopy and transmission electron microscopy results showed the engineered SOS structures.IBU and the carriers EC and PEG had good compatibility,as suggested by X-ray difraction and Fourier transform infrared spectroscopy assessments.In vitro dissolution tests verifed that the SOS products were able to provide a typical biphasic release profle,releasing 40%of the loaded IBU within 1 h in an immediate manner in the frst phase,and the rest of the IBU in a sustained manner in the second phase.A combined mechanism of erosion and difusion is proposed for manipulating the IBU molecule release behaviors.
