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pH sensitive liposome

Yang Cheng, Tao Zou, Min Dai, Xiao-Yan He, Na Peng, Kui Wu, Xiao-Qiang Wang, Cheng-Yun Liao, Yi Liu
Ammonium bicarbonate (ABC) liposomes can only release drugs extracellularly while intracellular drug delivery could be more promising than extracellular release in chemotherapy. The purpose of this work was to endow the ABC liposomes with tumor-triggered targeting effect, to realize the intracellular drug release and retain the long circulation characteristics of the liposomes. The tumor-triggered targeting ABC (TT-ABC) liposomes were proposed to improve uptake of tumor cells owing to folate (FA) - specific binding...
March 2, 2019: Colloids and Surfaces. B, Biointerfaces
Jacinta O Pinho, Joana D Amaral, Rui E Castro, Cecília Mp Rodrigues, Angela Casini, Graça Soveral, Maria Manuela Gaspar
AIM: Preclinical evaluation of a cytotoxic copper(II) complex formulated in long circulating nanoliposomes for melanoma treatment. MATERIALS & METHODS: Liposomal nanoformulations of the copper complex were characterized in terms of thermodynamic behavior (differential scanning calorimeter), pH-sensitivity (spectrophotometry) and antiproliferative effects against murine melanoma B16F10 cells in vitro. Preclinical studies were performed in a C57BL/6 syngeneic melanoma model...
March 15, 2019: Nanomedicine
Yu Huang, Li Yu, Jie Ren, Boram Gu, Colin Longstaff, Alun D Hughes, Simon A Thom, Xiao Yun Xu, Rongjun Chen
It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6 ± 5.3 nm in diameter) for selective thrombolysis through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets...
February 23, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Anastasia Yu Lokova, Olga V Zaborova
Purpose: Nowadays, the development of stimuli-sensitive nanocontainers for targeted drug delivery is of great value. Encapsulation of a drug in a pH-sensitive liposomal container not only provides protective and transport functions, but also helps to create a system with a controlled release mechanism. Methods: In this study, we investigated the influence of a cationic polypeptide on the pH-induced release of anticancer drug doxorubicin (DXR) from the anionic fliposomes - liposomes consisting of a neutral lipid, an anionic lipid (prone to interact with a polycation), and a lipid trigger (imparting the pH-sensitivity)...
2019: International Journal of Nanomedicine
Sara G T Pereira, Samo Hudoklin, Mateja Erdani Kreft, Nina Kostevsek, Marc C A Stuart, Wafa T Al-Jamal
L-377,202 prodrug (Dox-PSA) was in phase I Clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC). It consists of doxorubicin (Dox) conjugated to a prostate specific antigen (PSA)-cleavable peptide that can be selectively activated by secreted PSA at the tumour site. However, despite the initial promising results, further clinical testing with Dox-PSA was halted due to toxicity concerns emerging from non-PSA-specific cleavage, following systemic administration. In the present study, we have reported, and for the first time, the intracellular activation of Dox-PSA, where Dox nuclear uptake was specific to C4-2B (PSA-expressing) cells, which agreed with the cytotoxicity studies...
February 25, 2019: Molecular Pharmaceutics
Qiying Shen, Yurun Shen, Feiyang Jin, Yongzhong Du, Xiaoying Ying
Multidrug resistance (MDR) is the largest obstacle to the success of chemotherapy. The development of innovative strategies and safe sensitizers are required to overcome MDR. Paclitaxel (PTX) is a widely used chemotherapeutic drug, the application of which has been learn to understand MDR. However, the application and use are severely restricted because of this MDR. Cyclodextrins (CDs) of many carriers, additionally have shown anti-cancer capability in MDR cancer cells. In this study, novel paclitaxel/hydroxypropyl-β-cyclodextrin complex-loaded liposomes (PTXCDL) have been developed in an attempt to overcome MDR in a PTX-resistant human lung adenocarcinoma (A549/T) cell line...
February 10, 2019: Journal of Liposome Research
Dongdong Bi, Lei Zhao, Haowen Li, Yifei Guo, Xiangtao Wang, Meihua Han
Polydopamine (PDA) has been a simple, novel and versatile method to prepare targeted nanoparticles, which can be used as a platform for conjugating targeted ligands to polymer carriers without reactive chemical groups. To better understand the difference between the novel PDA method and conventional chemical synthesis way, we developed two kinds of folate (FA)-targeted liposomes loaded Doxorubicin (DOX) by the above methods. FA-PDA-DOX liposomes and DOX-FA liposomes represented PDA and conventional method, respectively...
January 21, 2019: International Journal of Pharmaceutics
Bingbing Li, Wei He, Ling Ye, Yuling Zhu, Yali Tian, Lian Chen, Jun Yang, Mingxing Miao, Yejiao Shi, Helena S Azevedo, Zhengliang Ma, Kun Hao
Pulmonary arterial hypertension is a fatal lung disease caused by the progressive remodeling of small pulmonary arteries (PAs). Sildenafil can prevent the remodeling of PAs, but conventional sildenafil formulations have shown limited treatment efficacy for their poor accumulation in PAs. Here, glucuronic acid (GlcA)-modified liposomes (GlcA-Lips) were developed to improve the delivery of sildenafil to aberrant over-proliferative PA smooth muscle cells via targeting the GLUT-1 (glucose transport-1), and, therefore, inhibiting the remodeling of PAs in a monocrotaline-induced PA hypertension model...
March 2019: Hypertension
Man Li, Yuting Yang, Chaoqun Xu, Jiaojie Wei, Yingke Liu, Xingli Cun, Qianwen Yu, Xian Tang, Sheng Yin, Zhirong Zhang, Qin He
Chemoimmunotherapy with chemotherapeutics and immunoadjuvant inhibits tumor growth by activating cytotoxic T cells. However, this process also upregulates the expression of PD-1/PD-L1 and consequently leads to immune suppression. To maximize the anti-tumor immune responses and alleviate immunosuppression, PD-L1 antibody was combined with paclitaxel (PTX) and the immunoadjuvant α-galactosylceramide (αGC), which were coencapsulated into pH-sensitive TH peptide-modified liposomes (PTX/αGC/TH-Lip) to treat melanoma and lung metastasis...
January 11, 2019: AAPS Journal
Ya Liu, Zeng-Ying Qiao, Pei-Pei Yang, Hao Wang, Xiguang Chen
Despite recent advances in tumor treatment through cancer immunotherapy, the efficacy of this method remains to be improved. Looking forward to high rates of objective clinical response, cancer immunotherapy combined with chemotherapy has gained increasing attention recently. Here, we constructed liposomes with matrix metalloproteinases (MMPs) responsive moiety and PD-L1 inhibitor conjugate combine with low dose chemotherapy to achieve enhanced anti-tumor efficacy. Upon introduction of the pH-responsive polymer to LPDp, the co-assembly could be almost stable in physiological condition and tumor microenvironment and release the loaded cargos at the lysosome...
January 8, 2019: Biomacromolecules
Jiaoyang Tao, Weidong Fei, Hongxia Tang, Chaoqun Li, Chaofeng Mu, Hongyue Zheng, Fanzhu Li, Zhihong Zhu
The poor capability of drugs to permeate through blood brain barrier (BBB) and further release inside glioma greatly limit the curative effects of glioma chemotherapies. In this study, we prepared angiopep-2 conjugated liposome-silica hybrid nanovehicles for targeted delivery and increased the permeation of arsenic trioxide (ATO) in glioma. Polyacrylic acid (PAA) was grafted on mesoporous silica nanoparticles (MSN) for pH-sensitive release and supporting lipid membrane. The prepared "core-shell" nanovehicles (ANG-LP-PAA-MSN) were characterized with uniform size, high drug loading efficiency (8...
January 8, 2019: Molecular Pharmaceutics
Mingmao Chen, Feifei Song, Yan Liu, Jia Tian, Chun Liu, Ruyue Li, Qiqing Zhang
In cancer therapy, chemotherapeutic drugs frequently encounter multidrug resistance (MDR) induced by the overexpression of drug transporters such as P-glycoprotein (P-gp). Herein, in order to overcome MDR and improve the effectiveness of chemotherapy, we developed a novel pH-sensitive charge-reversal and NO generation liposomal system by modifying a pH-sensitive polymer (PEG-PLL-DMA) on the surface of cationic liposomes for delivering a NO donor (DETA NONOate) and a chemotherapy drug (paclitaxel, PTX) into MDR cells...
January 2, 2019: Nanoscale
Soumyarwit Manna, Yong Wu, Yan Wang, Bonhye Koo, Lynn Chen, Peter Petrochenko, Yixuan Dong, Stephanie Choi, Darby Kozak, Berk Oktem, Xiaoming Xu, Jiwen Zheng
The mechanism of drug release from complex dosage forms, such as multivesicular liposomes (MVLs), is complex and oftentimes sensitive to the release environment. This challenges the design and development of an appropriate in vitro release test (IVRT) method. In this study, a commercial bupivacaine MVL product was selected as a model product and an IVRT method was developed using a modified USP 2 apparatus in conjunction with reverse-dialysis membranes. This setup allowed the use of in situ UV-Vis probes to continuously monitor the drug concentration during release...
January 28, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tatyana I Rokitskaya, Ljudmila S Khailova, Anton V Makarenkov, Alexei V Shunaev, Victor V Tatarskiy, Alexander A Shtil, Valentina A Ol'shevskaya, Yuri N Antonenko
Boron containing polyhedra (carboranes) are three-dimensional delocalized aromatic systems. These structures have been shown to transport protons through lipid membranes and mitochondria. Conjugation of carboranes to various organic moieties is aimed at obtaining biologically active compounds with novel properties. Taking advantage of 1,2,3-triazoles as the scaffolds valuable in medicinal chemistry, we synthesized 1-(o-carboranylmethyl)-4-pentyl-1,2,3-triazole (c-triazole) and 1-(o-carboranylmethyl)-4-pentyl-1,2,3-triazolium iodide (c-triazolium)...
December 15, 2018: Biochimica et Biophysica Acta. Biomembranes
Gianluca Toniolo, Maria Louka, Georgia Menounou, Nicolò Zuin Fantoni, George Mitrikas, Eleni K Efthimiadou, Annalisa Masi, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi, Andrew Kellett, Carla Ferreri, Chryssostomos Chatgilialoglu
The use of copper complexes for redox and oxidative-based mechanisms in therapeutic strategies is an important field of multidisciplinary research. Here, a novel Cu(II) complex [Cu(TPMA)(Phen)](ClO4 )2 (Cu-TPMA-Phen, where TPMA = tris-(2-pyridylmethyl)amine and Phen = 1,10-phenanthroline) was studied using both the free and encapsulated forms. A hollow pH-sensitive drug-delivery system was synthesized, characterized, and used to encapsulate and release the copper complex, thus allowing for the comparison with the free drug...
November 30, 2018: ACS Omega
Maria Manconi, Maria Letizia Manca, Elvira Escribano-Ferrer, Elisabet Martí Coma-Cros, Arnau Biosca, Elena Lantero, Xavier Fernàndez-Busquets, Anna Maria Fadda, Carla Caddeo
In this paper, nutriosomes (phospholipid vesicles associated with Nutriose® FM06) were modified to obtain new systems aimed at enhancing the efficacy of curcumin in counteracting malaria infection upon oral administration. Eudragit® L100, a pH-sensitive co-polymer, was added to these vesicles, thus obtaining eudragit-nutriosomes, to improve their in vivo performances. Liposomes without eudragit and nutriose were also prepared as a reference. Cryo-TEM images showed the formation of multicompartment vesicles, with mean diameter around 300 nm and highly negative zeta potential...
December 7, 2018: International Journal of Pharmaceutics
Tianqun Lang, Yiran Liu, Zhong Zheng, Wei Ran, Yihui Zhai, Qi Yin, Pengcheng Zhang, Yaping Li
Metastatic breast cancer may be resistant to chemo-immunotherapy due to the existence of cancer stem cells (CSC). And the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti-CSC agent thioridazine (THZ), and the PD-1/PD-L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure...
December 5, 2018: Advanced Materials
Federica Rinaldi, Patrizia N Hanieh, Elena Del Favero, Valeria Rondelli, Paola Brocca, Mohan C Pereira, Oleg A Andreev, Yana K Reshetnyak, Carlotta Marianecci, Maria Carafa
Acidity at surface of cancer cells is a hallmark of tumor microenvironments, which does not depend on tumor perfusion, thus it may serve as a general biomarker for targeting tumor cells. We used the pH (low) insertion peptide (pHLIP) for decoration of liposomes and niosomes. pHLIP senses pH at the surface of cancer cells and inserts into the membrane of targeted cells, and brings nanomaterial to close proximity of cellular membrane. DMPC liposomes and Tween 20 or Span 20 niosomes with and without pHLIP in their coating were fully characterized in order to obtain fundamental understanding on nanocarrier features and facilitate the rational design of acidity sensitive nanovectors...
December 4, 2018: Nanoscale Research Letters
Jingjing Liu, Longlong Tian, Rui Zhang, Ziliang Dong, Hairong Wang, Zhuang Liu
The abundant tumor extracellular matrix (ECM) could result in the insufficient tumor retention and ineffective intra-tumor penetration of therapeutic agents, as well as acidic & hypoxic tumor microenvironment (TME), further leading to the unsatisfactory therapeutic outcomes for many types of therapies. Therefore, developing strategies to modulate the TME by selectively degrading the condensed ECM may be helpful to improve existing cancer therapies. Herein, collagenase (CLG) encapsulated nanoscale coordination polymers (NCPs) are synthesized based on Mn2+ and an acid-sensitive benzoic-imine organic linker, and then modified by polyethylene glycol (PEG)...
November 23, 2018: ACS Applied Materials & Interfaces
Bibo Li, Biqiang Li, Daiying He, Changyan Feng, Zhibin Luo, Mei He
BACKGROUND: The use of misonidazole (MISO), the first and a potential hypoxic tumor cell radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials. OBJECTIVE: To develop a targeted drug delivery and tracing system with pH-sensitive liposomes (SpHLs) and superparamagnetic iron oxide nanoparticles (SPIONs) to counter MISO-related adverse effects and to enable tracing under magnetic resonance. METHODS: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method...
November 14, 2018: Current Drug Delivery
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