Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which...Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.展开更多
The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important r...The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.展开更多
Pulmonary drug delivery has attracted increasing attention in biomedicine,and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs.However,the existing methods for prepa...Pulmonary drug delivery has attracted increasing attention in biomedicine,and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs.However,the existing methods for preparing porous particles using porogens have several drawbacks,such as the inhomogeneous and uncontrollable pores,drug leakage,and high risk of fragmentation.In this study,a series of cyclodextrin-based metal-organic framework(CD-MOF)particles containing homogenous nanopores were delicately engineered without porogens.Compared with commercial inhalation carrier,CDMOF showed excellent aerosolization performance because of the homogenous nanoporous structure.The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments,including cytotoxicity assay,hemolysis ratio test,lung function evaluation,in vivo lung injury markers measurement,and histological analysis.The results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in lungs.Therefore,all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery.This study may throw light on the nanoporous particles for effective pulmonary administration.展开更多
基金supported by Pearl River S&T Nova Program of Guangzhou(2014J2200082)
文摘Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.
基金This work was financially supported by the National Natural Science Foundation of China(No.81803466)the Natural Science Foundation of Guangdong Province(No.2018A030310095,China)the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002,China).
文摘The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.
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,China)+1 种基金the National Science and Technology Major Program(Grant No.2017zx09101001,China)Natural Science Foundation of Guangdong Province(Grant No.2018A030310095,China)
文摘Pulmonary drug delivery has attracted increasing attention in biomedicine,and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs.However,the existing methods for preparing porous particles using porogens have several drawbacks,such as the inhomogeneous and uncontrollable pores,drug leakage,and high risk of fragmentation.In this study,a series of cyclodextrin-based metal-organic framework(CD-MOF)particles containing homogenous nanopores were delicately engineered without porogens.Compared with commercial inhalation carrier,CDMOF showed excellent aerosolization performance because of the homogenous nanoporous structure.The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments,including cytotoxicity assay,hemolysis ratio test,lung function evaluation,in vivo lung injury markers measurement,and histological analysis.The results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in lungs.Therefore,all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery.This study may throw light on the nanoporous particles for effective pulmonary administration.