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pH sensitive liposome

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
Yi Chen, Qianming Du, Qianqian Guo, Jing Huang, Lina Liu, Xiangchun Shen, Jianqing Peng
The CaCO3 encapsulated liposome with pH sensitivity is an efficient carrier for the delivery of chemotherapeutic drugs. Herein, we provided an innovative method that take advantage of a W/O emulsion to prepare CaCO3 encapsulated liposomes for the delivery of curcumin. The liposomes with both CaCO3 and curcumin encapsulated (LCC) showed highly sensitivity to reduced pH (the environment of lysosomes). Due to the inherent pH sensitivity of CaCO3 , LCC swelled and released the encapsulated curcumin rapidly in acidic medium...
October 22, 2018: Drug Development and Industrial Pharmacy
Francesca Sacchetti, Gaetano Marverti, Domenico D'Arca, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Salvatore Pacifico, Glauco Ponterini, Maria Paola Costi, Eliana Leo
PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition...
September 12, 2018: Pharmaceutical Research
Man Li, Yuting Yang, Jiaojie Wei, Xingli Cun, Zhengze Lu, Yue Qiu, Zhirong Zhang, Qin He
Cholesterol facilitated the formation of T cell receptor on cytotoxic CD8+ T lymphocytes (CTLs). However, the activation of CD8+ T cells always resulted in the upregulation of acetyl-CoA acetyltransferase-1 (ACAT-1) and enhanced the esterification of cholesterol. To relieve the suppression on CD8+ T cells, an ACAT-1 inhibitor avasimibe was combined with chemo-immunotherapy. Paclitaxel and immunoadjuvant αGC were co-encapsulated in liposomes modified with pH sensitive TH peptide (PTX/αGC-TH-Lip). After intravenous injections, the combination of avasimibe significantly elevated the free cholesterol level and relieved the inhibition of CD8+ T cells caused by PTX/αGC-TH-Lip, leading to enhanced CTL responses and anti-tumor effects of PTX/αGC-TH-Lip in B16F10 melanoma xenograft and lung metastasis models...
November 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Magdalini Rovoli, Ioannis Pappas, Stavros Lalas, Olga Gortzi, George Kontopidis
Vitamin A (VA) is an essential nutrient needed in small amounts by humans and supports a wide range of biological actions. Retinol, the most common and most biologically active form of VA has also been found to inhibit peroxidation processes in membranes and it has been widely used as an ingredient with pharmaceutical and nutritional applications. VA is a lipophilic molecule, sensitive to air, oxidizing agents, ultraviolet light and low pH levels. For these reasons, it is necessary for VA to be protected against oxidation...
September 6, 2018: Journal of Liposome Research
Shirleide Santos Nunes, Renata Salgado Fernandes, Carolina Henriques Cavalcante, Isabela da Costa César, Elaine Amaral Leite, Sávia Caldeira Araújo Lopes, Alice Ferretti, Domenico Rubello, Danyelle M Townsend, Mônica Cristina de Oliveira, Valbert Nascimento Cardoso, André Luís Branco de Barros
Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model...
September 5, 2018: Drug Delivery and Translational Research
Attila Bóta, András Wacha, Zoltán Varga, Imola Csilla Szigyártó, Sándor Kristyán, András Lőrincz, Pál Szabó, Miklós Kálmán, Lívia Naszályi-Nagy, Judith Mihály
Stable unilamellar dipalmitoylphosphatidylcholine vesicles were produced by using oligo(malic acid) and cholesterol. Detailed physico-chemical characterization prove that by using oligo(malic acid) the substitution of PEGylated lipids for sterically stabilization comes possible. The polymer molecules cover the outer surface of spherical-shaped vesicles, and an asymmetrical composition occurs in the two leaflets of the phospholipid bilayer. The oligo(malic-acid) and cholesterol are enriched in the outer side assuring the stabilization of vesicles...
December 15, 2018: Journal of Colloid and Interface Science
Zili Gu, Qingjie Wang, Yanbin Shi, Yi Huang, Jing Zhang, Xinke Zhang, Guimei Lin
Immunotherapy has exhibited enormous practice in the treatment of melanoma because of the intrinsic properties of tumor. Tumor can downmodulate immune function via multiple mechanisms such as immune checkpoint pathways. The PD-L1 monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells to evade an immune attack, can delay tumor growth efficiently with inevitable disadvantages such as low selectivity and systemic toxicity. Nanomedicine is clearly an approach that holds tremendous potential for addressing the shortcomings and assisting delivery of drugs with proper biodistribution...
September 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Mala Sharma, Chitranshu Pandey, Neha Sharma, M A Kamal, Usman Sayeed, Salman Akhtar
BACKGROUND: Nanotechnology pictures a breakthrough in the domain of cancer therapy owing to its novel properties and functions. This technology is quite amendable as it allows the scientists to engineer drug nanoparticles of dimensions 10nm - 500nm permitting them to pass via leaky vasculature of tumorigenic microenvironment with higher specificity, reduced cytotoxicity and effective release without any after effects. The central part of the review zooms onto the role of nanoparticles and their targeted delivery for the cure of cancer...
July 20, 2018: Anti-cancer Agents in Medicinal Chemistry
Nikolaos Naziris, Natassa Pippa, Dimitris Stellas, Varvara Chrysostomou, Stergios Pispas, Costas Demetzos, Marcin Libera, Barbara Trzebicka
Chimeric/mixed stimuli-responsive nanocarriers are promising agents for therapeutic and diagnostic applications, as well as in the combinatorial field of theranostics. Herein, we designed chimeric nanosystems, composed of natural phospholipid and pH-sensitive amphiphilic diblock copolymer, in different molar ratios and assessed the polymer lyotropic effect on their properties. Initially, polymer-grafted bilayers were evaluated for their thermotropic behavior by thermal analysis. Chimeric liposomes were prepared through thin-film hydration and the obtained vesicles were studied by light scattering techniques, to measure their physicochemical characteristics and colloidal stability, as well as by imaging techniques, to elucidate their global and membrane morphology...
July 20, 2018: AAPS PharmSciTech
Siyam M Ansar, Wenlei Jiang, Thilak Mudalige
To understand the quality, efficacy, and safety of liposomal drugs, it is necessary to develop a robust and accurate method for the separation and the quantification of unencapsulated and liposome-associated drugs (or liposomal encapsulated drugs). Conventional methods involve separation of unencapsulated and liposome-associated drug using solid phase extraction and further drug quantification. This is a lengthy process, and sometimes solid phase extraction induces drug leakage from the liposomes causing erroneous results...
October 5, 2018: International Journal of Pharmaceutics
Manju Kanamala, Brian D Palmer, William R Wilson, Zimei Wu
To facilitate the development of PEG-cleavable pH-sensitive liposomes (CL-pPSL), this study aimed to fully characterize a new pH-sensitive polymer, PEGB -Hz-CHEMS. Polyethylene glycol (PEG) functionalised with 4-carboxybenzaldehyde (PEGB ) was linked to cholesteryl hemisuccinate (CHEMS) via an acid labile hydrazide-hydrazone hybrid bond (CONHNCH) to form PEGB -Hz-CHEMS. The polymer was post-inserted into DOPE/CHEMS liposomes to form CL-pPSL. A validated stability-indicating HPLC-UV method was developed with the aid of multiple linear regression for the mobile phase...
September 5, 2018: International Journal of Pharmaceutics
Yuqiong Xia, Mei Fang, Jingyu Dong, Chunzhong Xu, Zhen Liao, Pengbo Ning, Qi Zeng
Multidrug resistance of tumour cells is one of the most important hurdles in tumour chemotherapy. To overcome the multidrug resistance, we constructed a pH-sensitive liposome formulation (pHSL) by loading tariquidar (TQR) and DOX simultaneously in this work. The formulation showed high stability at pH 7.4 and excellent sensitivity at acidic pH, which facilitated the delivery of TQR and DOX into cells. Cellular experiments demonstrated that the pHSL/TQR/DOX 0.05 could almost restore the drug sensitivity of OVCAR8/ADR cells...
October 1, 2018: Colloids and Surfaces. B, Biointerfaces
Sijia Wang, Tong Wang, Junqi Zhang, Shouhong Xu, Honglai Liu
Antitumor peptides may potentially alleviate the problem of chemoresistance but do not yet target tumor cells and would be cytotoxic to normal cells. Here, we designed a pH-activated and thermosensitive lipopeptide (C6-Pep) containing a leucine zipper and an alkyl chain and assessed the ability of C6-Pep to kill cancer cells. Pep, the same sequence without the N-terminal hexanoic acid moiety, was generated as a less hydrophobic control. First, lipopeptide adsorption into lipid monolayers was studied using Langmuir-Blodgett and polarization modulation infrared reflection adsorption spectroscopy...
July 31, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Juliana de Oliveira Silva, Sued Eustáquio Mendes Miranda, Elaine Amaral Leite, Adriano de Paula Sabino, Karina Braga Gomes Borges, Valbert Nascimento Cardoso, Geovanni Dantas Cassali, Andrea Grabe Guimarães, Mônica Cristina Oliveira, André Luis Branco de Barros
Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX)...
August 1, 2018: Toxicology and Applied Pharmacology
Yi-Ting Chiang, Sih-Ying Lyu, Yu-Han Wen, Chun-Liang Lo
pH-sensitive polymer⁻liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer⁻liposomes. In this study, stable and pH-sensitive crosslinked polymer⁻liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)- block -poly(methacrylic acid)-cholesterol (mPEG- b -P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized...
May 30, 2018: International Journal of Molecular Sciences
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