<span style="font-family:Verdana;"><strong>Background</strong></span><b><span style="font-family:Verdana;">:</span></b><span style="font-fami...<span style="font-family:Verdana;"><strong>Background</strong></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> Inappropriate disposal practices of medicinal products by households can harm nature. Alternatively, passing unused medications to friends and family members can have undesirable consequences as the quality of the product is in question.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Objective</span></b><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> To investigate the disposal and recycling practices of medicinal products by households in Saudi Arabia. </span><b><span style="font-family:Verdana;">Methods</span></b></span><span style="font-family:Verdana;">:</span><span style="font-family:""><span style="font-family:Verdana;"> A cross-sectional questionnaire designed to investigate disposal and recycling practices aimed at households in Saudi Arabia. Phone interviews were conducted with healthcare providers from hospitals and community pharmacies as well as medical charity representatives. A thorough search (Jun-September 2020) for disposal and recycling policies was performed on the Saudi Food and Drug Authority (SFDA) and the Ministry of Health websites.</span><b><span style="font-family:Verdana;"> Results</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> More than 900 participants were included in this study. Approximately 40% of respondents claimed to follow the SFDA recommendations for </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">disposal of unwanted medications in the wastebasket, whilst </span><span style="font-family:""><span style="font-family:Verdana;">≥</span><span style="font-family:Verdana;">6% preferred disposal via the toilet. On the other hand, 10% and 5% of households donated their unwanted over-the-counter and prescription</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">only medication products, respectively, to a person in need, without referring to healthcare professionals. Interviews with healthcare providers and medical charities revealed no drug take-back programs were currently available for households. The SFDA website provides a brief guide on</span><span style="font-family:Verdana;"> the</span><span style="font-family:Verdana;"> disposal of unwanted or expired medication.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Conclusions</span></b><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> The absence of a clear drug disposal policy for households has created a gap allowing incorrect disposal practices that may lead to harming patients and/or the environment. The launching of drug take-back programs may lead to the provision of a clear consensus of governing bodies and healthcare providers on patient guidance for a safe drug disposal policy.</span>展开更多
As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,t...As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.展开更多
Programmed release of small molecular drugs from polymersomes is of great importance in drug delivery.A significant challenge is to adjust the membrane permeability in a well-controlled manner.Herein,we propose a stra...Programmed release of small molecular drugs from polymersomes is of great importance in drug delivery.A significant challenge is to adjust the membrane permeability in a well-controlled manner.Herein,we propose a strategy for controlling membrane phase separation by photo-cross-linking of the membrane-forming blocks with different molecular architectures.We synthesized three amphiphilic block copolymers with different membrane-forming blocks,which are poly(ethylene oxide)_(43)-b-poly((ε-caprolactone)_(45)-stat-((α-(cinnamoyloxymethyl)-1,2,3-triazol)caprolactone)_(25))(PEO_(43)-b-P(CL_(45)-stat-CTCL_(25))),PEO_(43)-b-P(CL_(108)-stat-CTCL_(16)),and PEO_(43)-b-PCTCL_(4)-b-PCL_(79).These polymers were self-assembled into polymersomes using either a solvent-switch or powder rehydration method,and the obtained polymersomes were characterized by dynamic light scattering and transmission electron microscopy.Then the phase separation patterns within the polymersome membranes were investigated by mesoscopic dynamics(MesoDyn)simulations.To further confirm the change of the membrane permeability that resulted from the phase separation within the membrane,doxorubicin,as a small molecular drug,was loaded and released from the polymersomes.Due to the incompatibility between membrane-forming moieties(PCTCL and PCL),phase separation occurs and the release rate can be tuned by controlling the membrane phase pattern or by photo-cross-linking.Moreover,besides the compacting effect by formation of chemical bonds in the membrane,the cross-linking process can act as a driving force to facilitate the rearrangement and re-orientation of the phase pattern,which also influences the drug release behavior by modulating the cross-membrane distribution of the amorphous PCTCL moieties.In this way,the strategy of focusing on the membrane phase separation for the preparation of the polymersomes with finely tunable drug release rate can be envisioned and designed accordingly,which is of great significance in the field of delivery vehicles for programmed drug release.展开更多
In 2018,the Chinese government identified four municipalities and seven sub-provincial cities for the implementation of the National Drug Pooled Procurement(NDPP)pilot program(the“4+7”policy).In the present study,we...In 2018,the Chinese government identified four municipalities and seven sub-provincial cities for the implementation of the National Drug Pooled Procurement(NDPP)pilot program(the“4+7”policy).In the present study,we analyzed the effects of the“4+7”policy with data of 25 pilot drugs from the National Healthcare Security Administration(NHSA)from the aspects of drug price,volume,and expenditure.After the implementation of the policy,the average price of total and winning drugs was decreased by 54.47%and 73.82%,respectively,while the DDDc of non-winning drugs was decreased by only 1.54%,and the DDDc of uncertificated generic drugs was increased 83.18%.The DDDs indicating the volume of total and winning drugs was increased by 21.18%and 353.98%,respectively,and the DDDs of non-winning drugs was decreased by 61.35%.The costs of total and non-winning drugs were decreased by 44.83%and 61.94%,respectively,and the cost of winning drugs was increased by 18.87%.The“4+7”policy reduced the price and cost of pilot drugs and improved the affordability and accessibility of drugs.However,there were also problems with unexpected excessive price increases of uncertificated generic drugs and relatively high prices of non-winning products.Therefore,we highly suggested promoting the normalization and institutionalization of pooled drug procurement,enhancing the administrative capacity of local procurement platforms,and strengthening monitoring the price of non-winning,especially for the uncertificated generic drugs.展开更多
Combination therapy is one of the potential strategies for tackling complicated tumor treatments like drug resistance.In this work,we have generated a therapeutic cisplatin-crosslinked albumin hydrogel(BC-Gel)that all...Combination therapy is one of the potential strategies for tackling complicated tumor treatments like drug resistance.In this work,we have generated a therapeutic cisplatin-crosslinked albumin hydrogel(BC-Gel)that allows the local release of L-Buthionine-sulfoximine(BSO),cisplatin,and glucose oxidase(GOx)with distinct release kinetics.The BC-Gel with favorable biostimuli degradability and injectability could release therapeutic agents in a programmed manner within the tumor microenvironment(TME).The preferentially released BSO significantly suppressed the glutathione(GSH)-related cisplatin resistance and sensitized the tumor cells to cisplatin by inhibiting theγ-glutamylcysteine synthetase.Meanwhile,cisplatin achieved a sequential release and long-term treatment following the bioresponsive gel degradation under the combined action of chloride ions(Cl−)and proteinase in the body.In addition,the overproduced H_(2)O_(2)of GOx-catalyzed glucose oxidation accelerated the depletion of existed GSH within cells and further weakened the cisplatin resistance,achieving enhanced tumor treatment together with a strong cell-killing effect.The above sequential drug release strategy based on the dual GSH depletion effect breaks the balance of the GSH-mediated redox TME and enhances the sensitivity of A549 cells to cisplatin forcefully,and provides a promising way for temporal control of drug release as well as efficient cancer combination therapy.展开更多
文摘<span style="font-family:Verdana;"><strong>Background</strong></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> Inappropriate disposal practices of medicinal products by households can harm nature. Alternatively, passing unused medications to friends and family members can have undesirable consequences as the quality of the product is in question.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Objective</span></b><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> To investigate the disposal and recycling practices of medicinal products by households in Saudi Arabia. </span><b><span style="font-family:Verdana;">Methods</span></b></span><span style="font-family:Verdana;">:</span><span style="font-family:""><span style="font-family:Verdana;"> A cross-sectional questionnaire designed to investigate disposal and recycling practices aimed at households in Saudi Arabia. Phone interviews were conducted with healthcare providers from hospitals and community pharmacies as well as medical charity representatives. A thorough search (Jun-September 2020) for disposal and recycling policies was performed on the Saudi Food and Drug Authority (SFDA) and the Ministry of Health websites.</span><b><span style="font-family:Verdana;"> Results</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> More than 900 participants were included in this study. Approximately 40% of respondents claimed to follow the SFDA recommendations for </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">disposal of unwanted medications in the wastebasket, whilst </span><span style="font-family:""><span style="font-family:Verdana;">≥</span><span style="font-family:Verdana;">6% preferred disposal via the toilet. On the other hand, 10% and 5% of households donated their unwanted over-the-counter and prescription</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">only medication products, respectively, to a person in need, without referring to healthcare professionals. Interviews with healthcare providers and medical charities revealed no drug take-back programs were currently available for households. The SFDA website provides a brief guide on</span><span style="font-family:Verdana;"> the</span><span style="font-family:Verdana;"> disposal of unwanted or expired medication.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Conclusions</span></b><b><span style="font-family:Verdana;">:</span></b><span style="font-family:Verdana;"> The absence of a clear drug disposal policy for households has created a gap allowing incorrect disposal practices that may lead to harming patients and/or the environment. The launching of drug take-back programs may lead to the provision of a clear consensus of governing bodies and healthcare providers on patient guidance for a safe drug disposal policy.</span>
基金the Natural Science Foundation of Hubei Province,China(2021CFB468)Sci-tech Innovation Foundation of Huazhong Agriculture University(2662020LXPY007)National Key Research and Development Program of China(2021YFD1400800).
文摘As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.
基金financially supported by the National Natural Science Fund for Distinguished Young Scholars (No. 21925505)Shanghai International Scientific Collaboration Fund (No. 21520710100)+2 种基金supported by the National Natural Science Foundation of China (No. 22101207)the China Postdoctoral Science Foundation (No. 2020M671197)International Postdoctoral Exchange Fellowship Program
文摘Programmed release of small molecular drugs from polymersomes is of great importance in drug delivery.A significant challenge is to adjust the membrane permeability in a well-controlled manner.Herein,we propose a strategy for controlling membrane phase separation by photo-cross-linking of the membrane-forming blocks with different molecular architectures.We synthesized three amphiphilic block copolymers with different membrane-forming blocks,which are poly(ethylene oxide)_(43)-b-poly((ε-caprolactone)_(45)-stat-((α-(cinnamoyloxymethyl)-1,2,3-triazol)caprolactone)_(25))(PEO_(43)-b-P(CL_(45)-stat-CTCL_(25))),PEO_(43)-b-P(CL_(108)-stat-CTCL_(16)),and PEO_(43)-b-PCTCL_(4)-b-PCL_(79).These polymers were self-assembled into polymersomes using either a solvent-switch or powder rehydration method,and the obtained polymersomes were characterized by dynamic light scattering and transmission electron microscopy.Then the phase separation patterns within the polymersome membranes were investigated by mesoscopic dynamics(MesoDyn)simulations.To further confirm the change of the membrane permeability that resulted from the phase separation within the membrane,doxorubicin,as a small molecular drug,was loaded and released from the polymersomes.Due to the incompatibility between membrane-forming moieties(PCTCL and PCL),phase separation occurs and the release rate can be tuned by controlling the membrane phase pattern or by photo-cross-linking.Moreover,besides the compacting effect by formation of chemical bonds in the membrane,the cross-linking process can act as a driving force to facilitate the rearrangement and re-orientation of the phase pattern,which also influences the drug release behavior by modulating the cross-membrane distribution of the amorphous PCTCL moieties.In this way,the strategy of focusing on the membrane phase separation for the preparation of the polymersomes with finely tunable drug release rate can be envisioned and designed accordingly,which is of great significance in the field of delivery vehicles for programmed drug release.
文摘In 2018,the Chinese government identified four municipalities and seven sub-provincial cities for the implementation of the National Drug Pooled Procurement(NDPP)pilot program(the“4+7”policy).In the present study,we analyzed the effects of the“4+7”policy with data of 25 pilot drugs from the National Healthcare Security Administration(NHSA)from the aspects of drug price,volume,and expenditure.After the implementation of the policy,the average price of total and winning drugs was decreased by 54.47%and 73.82%,respectively,while the DDDc of non-winning drugs was decreased by only 1.54%,and the DDDc of uncertificated generic drugs was increased 83.18%.The DDDs indicating the volume of total and winning drugs was increased by 21.18%and 353.98%,respectively,and the DDDs of non-winning drugs was decreased by 61.35%.The costs of total and non-winning drugs were decreased by 44.83%and 61.94%,respectively,and the cost of winning drugs was increased by 18.87%.The“4+7”policy reduced the price and cost of pilot drugs and improved the affordability and accessibility of drugs.However,there were also problems with unexpected excessive price increases of uncertificated generic drugs and relatively high prices of non-winning products.Therefore,we highly suggested promoting the normalization and institutionalization of pooled drug procurement,enhancing the administrative capacity of local procurement platforms,and strengthening monitoring the price of non-winning,especially for the uncertificated generic drugs.
基金supported by the National Natural Science Foundation of China(Nos.22075065,22161142015,and 22001054)the National Key R&D Program of China(Nos.2020YFA0908500 and 2018YFA0901600)the Research Startup Fund from Hangzhou Normal University(Nos.2019QDL025,2019QDL026,and 4095C5022121604).
文摘Combination therapy is one of the potential strategies for tackling complicated tumor treatments like drug resistance.In this work,we have generated a therapeutic cisplatin-crosslinked albumin hydrogel(BC-Gel)that allows the local release of L-Buthionine-sulfoximine(BSO),cisplatin,and glucose oxidase(GOx)with distinct release kinetics.The BC-Gel with favorable biostimuli degradability and injectability could release therapeutic agents in a programmed manner within the tumor microenvironment(TME).The preferentially released BSO significantly suppressed the glutathione(GSH)-related cisplatin resistance and sensitized the tumor cells to cisplatin by inhibiting theγ-glutamylcysteine synthetase.Meanwhile,cisplatin achieved a sequential release and long-term treatment following the bioresponsive gel degradation under the combined action of chloride ions(Cl−)and proteinase in the body.In addition,the overproduced H_(2)O_(2)of GOx-catalyzed glucose oxidation accelerated the depletion of existed GSH within cells and further weakened the cisplatin resistance,achieving enhanced tumor treatment together with a strong cell-killing effect.The above sequential drug release strategy based on the dual GSH depletion effect breaks the balance of the GSH-mediated redox TME and enhances the sensitivity of A549 cells to cisplatin forcefully,and provides a promising way for temporal control of drug release as well as efficient cancer combination therapy.