Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialy...Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialysis-ultrasound method. CS-SA polymers, CS-SA nanomicelles, and FF/CS-SA nanomicelles were characterized by FT-IR, TGA, and SEM. Results showed that the SA was grafted to the amino of CS by amide bond. CS-SA nanomicelles and FF/CS-SA nanomicelles were spherical, smooth without fold. The influence of different molar ratio of FF to CS-SA polymers on the encapsulation efficiency and drug-loading rate determined the best molar ratio that was 1：1.09. In vitro release experiments, drug release performance study found that hydrophobic drug releasing from FF/CS-SA nanomicelles presented sustainedrelease. In vitro bacteriostasis experiments, when the concentration was higher than 4.98 mg/mL, FF/CSSA nanomicelles had antibacterial action and a positive correlation with concentration. The results revealed that amphiphilic chitosan derivative nanomicelles were carriers with broad prospects, increasing solubility of hydrophobic drugs and presenting sustained release for hydrophobic drugs, which provided a new research idea for drug delivery and targeted drug delivery of hydrohobic drugs.展开更多
Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the c...Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.展开更多
A novel redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate(P_(5k)SSLV)was designed and synthesized.Thin-film hydration method was used to prepare DOX-l...A novel redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate(P_(5k)SSLV)was designed and synthesized.Thin-film hydration method was used to prepare DOX-loaded P_(5k)SSLV nanomicelle.To optimize the preparation technology,we investigate the effects of dosage,type of organic solvent,hydration temperature and time,and cryoprotectant on drug-loading content,encapsulation efficiency,particle size,and zeta potential.The mean particle size and zeta potential were determined by Zetasizer.The morphology of the P_(5k)SSLV-DOX nanomicelles was visualized by transmission electron microscopy.The drug-loading content and encapsulation efficiency of P_(5k)SSLV-DOX nanomicelle were investigated by UV.The drug-loading content,encapsulation efficiency,particle size,and zeta potential of the final optimized nanomicelles were 4.58%,97.20%,30.21 nm and -0.84 mV,respectively.In addition,the stability of nanomicelles was investigated,which included dilution stability and storage stability.The results showed that P_(5k)SSLV-DOX nanomicelle had good dilution stability and storage stability at 4℃.The preparation method of P_(5k)SSLV-DOX nanomicelle with thinfilm hydration method was practical and simple,which was valuable to be further studied.展开更多
[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determin...[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.展开更多
Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the cl...Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the clinical application of which is limited by serious adverse effects and drug resistance.In this work,biodegradable methoxy poly(ethylene glycol)-block-poly(lactic acid)(mPEG-PLA)nanomicelles co-delivering of DOX and apatinib(AP)(DOX-AP/m)was developed for lymphoma therapy.The average particle size of the self-assembled drug-loaded nano-micelle was 31.94 nm.It is revealed that AP can enhance the uptake of DOX by tumor cells.The in vivo and in vitro experimental results revealed that DOX-AP/m combination therapy could inhibit proliferation and promote apoptosis of lymphoma cells,and greatly suppress tumor growth.Our study indicated that DOX-AP/m might provide new insight and hold great potential in the treatment of lymphoma.展开更多
Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current r...Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.展开更多
基金the Science and Technology Development Project of Shandong Province(No.2012GNC11307)the People's Livelihood Science and Technology Project of Qingdao(NO.14232nsh)
文摘Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialysis-ultrasound method. CS-SA polymers, CS-SA nanomicelles, and FF/CS-SA nanomicelles were characterized by FT-IR, TGA, and SEM. Results showed that the SA was grafted to the amino of CS by amide bond. CS-SA nanomicelles and FF/CS-SA nanomicelles were spherical, smooth without fold. The influence of different molar ratio of FF to CS-SA polymers on the encapsulation efficiency and drug-loading rate determined the best molar ratio that was 1：1.09. In vitro release experiments, drug release performance study found that hydrophobic drug releasing from FF/CS-SA nanomicelles presented sustainedrelease. In vitro bacteriostasis experiments, when the concentration was higher than 4.98 mg/mL, FF/CSSA nanomicelles had antibacterial action and a positive correlation with concentration. The results revealed that amphiphilic chitosan derivative nanomicelles were carriers with broad prospects, increasing solubility of hydrophobic drugs and presenting sustained release for hydrophobic drugs, which provided a new research idea for drug delivery and targeted drug delivery of hydrohobic drugs.
基金supported by National Natural Science Foundation of China(No.82073830)Chongqing Natural Science Foundation(No.CSTB2022NSCQ-MSX1328).
文摘Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.
文摘A novel redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate(P_(5k)SSLV)was designed and synthesized.Thin-film hydration method was used to prepare DOX-loaded P_(5k)SSLV nanomicelle.To optimize the preparation technology,we investigate the effects of dosage,type of organic solvent,hydration temperature and time,and cryoprotectant on drug-loading content,encapsulation efficiency,particle size,and zeta potential.The mean particle size and zeta potential were determined by Zetasizer.The morphology of the P_(5k)SSLV-DOX nanomicelles was visualized by transmission electron microscopy.The drug-loading content and encapsulation efficiency of P_(5k)SSLV-DOX nanomicelle were investigated by UV.The drug-loading content,encapsulation efficiency,particle size,and zeta potential of the final optimized nanomicelles were 4.58%,97.20%,30.21 nm and -0.84 mV,respectively.In addition,the stability of nanomicelles was investigated,which included dilution stability and storage stability.The results showed that P_(5k)SSLV-DOX nanomicelle had good dilution stability and storage stability at 4℃.The preparation method of P_(5k)SSLV-DOX nanomicelle with thinfilm hydration method was practical and simple,which was valuable to be further studied.
基金Supported by Special Fund for Basic Scientific Research Business in Central Universities(2019NYB31)Scientific Research Funded Project of Southwest Minzu University(2023KYZZ06N).
文摘[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.
基金supported by the National Natural Science Foundation of China(Nos.32222046,82172630)。
文摘Lymphoma is a hematological malignancy with an increasing mortality rate.Nevertheless,the treatment strategy against lymphoma remains limited.Doxorubicin(DOX)is a broad-spectrum anti-tumor chemotherapeutic drug,the clinical application of which is limited by serious adverse effects and drug resistance.In this work,biodegradable methoxy poly(ethylene glycol)-block-poly(lactic acid)(mPEG-PLA)nanomicelles co-delivering of DOX and apatinib(AP)(DOX-AP/m)was developed for lymphoma therapy.The average particle size of the self-assembled drug-loaded nano-micelle was 31.94 nm.It is revealed that AP can enhance the uptake of DOX by tumor cells.The in vivo and in vitro experimental results revealed that DOX-AP/m combination therapy could inhibit proliferation and promote apoptosis of lymphoma cells,and greatly suppress tumor growth.Our study indicated that DOX-AP/m might provide new insight and hold great potential in the treatment of lymphoma.
基金supported by the Young Elite Scientists Sponsorship Program by CACM(No.2022-QNRC2-B12)the Key Project of Anhui Province Department of Education(No.2022AH050528)+2 种基金Anhui Province Key Laboratory(No.2024ZYFBAHKLA11)the Domestic Visiting Project of Anhui Province Department of Education(No.gxgnfx2022015)the National Nature Science Foundation of China(No.82003675).
文摘Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.
