This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine...This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.展开更多
Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and ...Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and around the world to develop cutting-edge and potent anti-leishmanial treatments.Even though numerous medications could be utilized to treat VL,the limitations of current treatments including their toxicity,cost,route of administration,and duration of doses,have contributed to the emergence of resistance.Combination therapy might be a better option due to its shorter duration,easier route of administration,and ability to extend the lifespan of individual drugs.However,there is a risk of not delivering both the drugs to the target site together,which can be overcome by the liposomal entrapment of those drugs and at a time knock an opportunity to reduce the dosage of amphotericin B if the combination drug provides a synergistic effect with it.Therefore,this review presents a novel strategy to fight against VL by introducing dual drug-loaded liposomes.展开更多
The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional...The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional methods,the advantages and drawbacks of the latest techniques were reviewed.In the light of developments in many relevant areas,a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods.However,there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed.Generally speaking,due to the introduction of these latest techniques,liposome preparation is now an improved procedure.These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.展开更多
目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头...目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头超声法制备脂质体ELE/CTX@LIP,并采用纳米粒径电位仪对其粒径及电位进行表征,采用高效液相色谱法(HPLC)测定ELE/CTX包封率及载药量;采用细胞增殖与活性检测法(CCK-8)检测ELE/CTX体外细胞增殖抑制活性;通过JMP Pro 16软件,以包封率为指标优化脂质体(ELE/CTX@LIP)工艺参数;通过体外细胞增殖抑制活性和体外细胞摄取,筛选最佳阳离子材料种类、含量与配比,在此基础上制备双靶向阳离子脂质体并表征其形态、粒径稳定性等,验证其对RG2胶质瘤细胞的细胞周期和细胞凋亡的影响。结果:ELE/CTX抗胶质瘤活性结果显示ELE/CTX分别对C6、RG2细胞具有更强的细胞增殖抑制活性;体外细胞增殖抑制活性和体外细胞摄取结果显示阳离子材料用量为总含量的0.10%;T7、精氨酸-甘氨酸-天冬氨酸三肽序列(cRGD)与磷脂最佳配比为1∶1∶50。T7/cRGD-ELE/CTX@CLIP[1,2-二油酰氧基-3-二甲基氨基丙烷(DlinMC3-DMA)]、T7/cRGD-ELE/CTX@CLIP[二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)]呈现多层次球状纳米结构,粒径分别为146.0 nm和111.3 nm,血清稳定性良好;体外细胞增殖抑制结果显示,与单靶向脂质体或双靶向非阳离子脂质体比较,T7/cRGD-ELE/CTX@CLIP在体外对胶质瘤细胞具有更高的细胞增殖抑制活性;T7/cRGD-ELE/CTX@CLIP影响胶质瘤细胞凋亡及周期,结果显示,ELE/CTX联用能通过脂质体载体能更加有效的激活细胞凋亡通道抑制胶质瘤细胞增殖,且使用T7/cRGD短肽及阳离子修饰后,增强了细胞凋亡诱导能力,ELE/CTX能有效将胶质瘤细胞周期阻滞于G2/M期,且经T7/cRGD靶向修饰后,效果增强。结论:ELE可以增强CTX抗胶质瘤疗效,ELE/CTX@LIP制备工艺参数稳定可行,结合体外药效试验初步揭示了T7/cRGD-ELE/CTX@CLIP抗胶质瘤作用机制。展开更多
基金Universiti Kebangsaan Malaysia’s research university grant scheme (DCP-2017- 003/4)。
文摘This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.
基金SKM gratefully acknowledges the support of Indian Council of Medical Research(ICMR),New Delhi,India(File No:6/9-7(308)/2023-ECD-II)RH acknowledges the SVMCM fellowship,West Bengal.
文摘Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and around the world to develop cutting-edge and potent anti-leishmanial treatments.Even though numerous medications could be utilized to treat VL,the limitations of current treatments including their toxicity,cost,route of administration,and duration of doses,have contributed to the emergence of resistance.Combination therapy might be a better option due to its shorter duration,easier route of administration,and ability to extend the lifespan of individual drugs.However,there is a risk of not delivering both the drugs to the target site together,which can be overcome by the liposomal entrapment of those drugs and at a time knock an opportunity to reduce the dosage of amphotericin B if the combination drug provides a synergistic effect with it.Therefore,this review presents a novel strategy to fight against VL by introducing dual drug-loaded liposomes.
文摘The article presents a review of new techniques being used for the preparation of liposomes.A total of 28 publications were examined.In addition to the theories,characteristics and problems associated with traditional methods,the advantages and drawbacks of the latest techniques were reviewed.In the light of developments in many relevant areas,a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods.However,there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed.Generally speaking,due to the introduction of these latest techniques,liposome preparation is now an improved procedure.These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.
文摘目的:探究榄香烯(ELE)增强卡巴他赛(CTX)抗胶质瘤疗效,制备一种共载ELE/CTX的双靶向阳离子脂质体(LIP)用于胶质瘤的治疗研究,并达到增加药效、减少不良反应的作用,经体外药效学试验揭露其优势及作用机制。方法:采用高速剪切法联合探头超声法制备脂质体ELE/CTX@LIP,并采用纳米粒径电位仪对其粒径及电位进行表征,采用高效液相色谱法(HPLC)测定ELE/CTX包封率及载药量;采用细胞增殖与活性检测法(CCK-8)检测ELE/CTX体外细胞增殖抑制活性;通过JMP Pro 16软件,以包封率为指标优化脂质体(ELE/CTX@LIP)工艺参数;通过体外细胞增殖抑制活性和体外细胞摄取,筛选最佳阳离子材料种类、含量与配比,在此基础上制备双靶向阳离子脂质体并表征其形态、粒径稳定性等,验证其对RG2胶质瘤细胞的细胞周期和细胞凋亡的影响。结果:ELE/CTX抗胶质瘤活性结果显示ELE/CTX分别对C6、RG2细胞具有更强的细胞增殖抑制活性;体外细胞增殖抑制活性和体外细胞摄取结果显示阳离子材料用量为总含量的0.10%;T7、精氨酸-甘氨酸-天冬氨酸三肽序列(cRGD)与磷脂最佳配比为1∶1∶50。T7/cRGD-ELE/CTX@CLIP[1,2-二油酰氧基-3-二甲基氨基丙烷(DlinMC3-DMA)]、T7/cRGD-ELE/CTX@CLIP[二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)]呈现多层次球状纳米结构,粒径分别为146.0 nm和111.3 nm,血清稳定性良好;体外细胞增殖抑制结果显示,与单靶向脂质体或双靶向非阳离子脂质体比较,T7/cRGD-ELE/CTX@CLIP在体外对胶质瘤细胞具有更高的细胞增殖抑制活性;T7/cRGD-ELE/CTX@CLIP影响胶质瘤细胞凋亡及周期,结果显示,ELE/CTX联用能通过脂质体载体能更加有效的激活细胞凋亡通道抑制胶质瘤细胞增殖,且使用T7/cRGD短肽及阳离子修饰后,增强了细胞凋亡诱导能力,ELE/CTX能有效将胶质瘤细胞周期阻滞于G2/M期,且经T7/cRGD靶向修饰后,效果增强。结论:ELE可以增强CTX抗胶质瘤疗效,ELE/CTX@LIP制备工艺参数稳定可行,结合体外药效试验初步揭示了T7/cRGD-ELE/CTX@CLIP抗胶质瘤作用机制。
