Multifunctionality of lipid-core micelles for drug delivery and tumour targeting

Abstract

Phospholipid micelles have proven to be the versatile pharmaceutical nanocarrier of choice for the delivery of poorly soluble chemotherapeutics for cancer therapy using various treatment modalities. Phospholipid micelles are typically expected to increase the accumulation of the loaded drugs in tumour tissues by taking advantage of the enhanced permeability and retention effect and by ligand-mediated active targeting. Furthermore, by tailoring the composition of the micelles, it is possible to enhance the intracellular delivery of the cargo. This review highlights the important advancements in our laboratory with polyethyleneglycol phosphatidylethanolamine (PEG-PE)-based micellar drug delivery systems for improvement of the therapeutic efficacy of poorly soluble anticancer drugs.     

Nanostructured lipid carriers as semisolid topical delivery formulations for diflucortolone valerate

Context: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption.

Objective: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption.

Method: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol? or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs.

Results and discussion: DFV-loaded NLC formulations possessed average particle size ranging from 160.40?nm to 743.7?nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12?h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation.

Conclusion: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.     

纳米递送系统线粒体靶向策略在肿瘤诊疗中的应用

肿瘤是危害人类健康的重大疾病之一。目前用于肿瘤治疗的方法有手术治疗、化学药物治疗、放射治疗等。然而,传统的治疗方法存在治疗效果不佳、易引发多药耐药、毒副作用大等缺点,仍需进一步探索新的肿瘤治疗靶点和策略。线粒体作为细胞的能量转换器,被认为是肿瘤、心血管和神经性疾病新药设计的最重要靶点之一。纳米药物递送载体具有易被主动靶向基团修饰的特点,可实现细胞乃至细胞器的精准靶向给药。本文从抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤复发与转移、诱导细胞自噬等方面综述了线粒体靶向纳米载体在肿瘤诊疗中的应用。     

Nanocarriers for combating biofilms: Advantages and challenges

Bacterial biofilms are highly resistant to antibiotics and pose a great threat to human and animal health. The control and removal of bacterial biofilms have become an important topic in the field of bacterial infectious diseases. Nanocarriers show great anti-biofilm potential because of their small particle size and strong permeability. In this review, the advantages of nanocarriers for combating biofilms are analysed. Nanocarriers can act on all stages of bacterial biofilm formation and diffusion. They can improve the scavenging effect of biofilm by targeting biofilm, destroying extracellular polymeric substances and enhancing the biofilm permeability of antimicrobial substances. Nanocarriers can also improve the antibacterial ability of antimicrobial drugs against bacteria in biofilm by protecting the loaded drugs and controlling the release of antimicrobial substances. Additionally, we emphasize the challenges faced in using nanocarrier formulations and translating them from a preclinical level to a clinical setting.     

Optimizing efficacy of amphotericin B through nanomodification

Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB- deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical efficacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifications of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specific drug delivery.     

间充质干细胞来源的外泌体的特性及其在疾病治疗中的作用

外泌体(exosomes)是细胞主动向外环境中分泌的纳米囊泡结构,通常直径在100纳米以下。外泌体是来源细胞与靶细胞之间的物质交换和信息交流的新型载体,可以携带效应分子直接被周围细胞摄取或经血液循环至全身,在正常的生理过程或疾病的发生发展中发挥精细的调控作用。作为一种旁分泌介质,间充质干细胞(mesenchymal stem cell, MSC）来源的外泌体(MSC-exosomes)能够起到与干细胞相似的生理作用。MSC-exosomes所携带的生物活性蛋白质、脂质及DNA、mRNA和非编码RNA等生物活性物质,可能是MSC发挥治疗作用的重要机制之一。本文针对外泌体的生物学来源和近年来MSC-exosomes的标志物与特异性内容物在产生释放、提取鉴定和生物学功能等方面的研究,以及未来的应用前景进行综述,有利于研究者们在该领域开展更深入的研究。     

刺激响应型纳米载体在肿瘤诊疗中的研究进展

刺激响应型纳米载体是通过对外界刺激响应而产生相应结构或理化性质变化的纳米智能载药体系,具有避免药物过早泄露,提高病灶药物浓度的特点,目前已成为肿瘤诊断和治疗领域的研究热点,广泛用于控制药物的呈递和释放.本文从温度、磁场、超声、光、pH等外源和内源刺激角度,阐述了智能响应型纳米载体近年来在肿瘤诊疗领域的研究进展.     

Preparation of novel cisplatin-conjugated hollow gold nanospheres for targeting cervical cancer

Cervical cancer is a deadly gynecological malignancy in need of innovative treatment strategies. Emerging preclinical data has suggested the benefits of nanocarriers over the traditional chemotherapy for cancer treatment. In particular, gold nanoparticles are gaining popularity due to gold's inert nature, limited side effects, good cytocompatibility, and flexibility in preparation/modification. We conjugated polyethylene glycol (PEG) with hollow gold nanospheres (HGNs) and loaded the pegylated HGNs with an anticancer drug, cisplatin to target cervical cancer. HGNs were irradiated with noninfrared laser to increase the penetration of drug into tumor tissue and improve the delivery of cisplatin. We investigated the comparative characterization studies of prepared cisplatin loaded pegylated HGNs (cis PEG-HGNs), free cisplatin, cisplatin loaded HGNs (cis-HGNs), cis PEG-HGNs without laser, and cis PEG-HGNs with laser and its effects over cervical cancer cells. Transmission electron microscopy photomicrographs confirmed the integrity of prepared HGNs. While no significant difference was observed between encapsulation efficiency and drug loading of cis-HGNs (84.6%) and cis PEG-HGNs (86.7%), the encapsulation efficiency increased almost twice in HGNs, compared with control gold nanoparticles (GNs) because of the hollow cavity in HGNs. In-vitro cytotoxicity was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using HeLa cells. With irradiation, HGNs induced much elevated cytotoxicity. Not only HGNs were internalized by HeLa cells, they were retained in the cellular compartment. We also tested formulations in vivo and observed that the irradiated cis-HGNs and cis PEG-HGNs were most effective in regressing tumors in mice.     

基于酸敏感的双响应抗癌药物载体的研究进展

为了达到更好的肿瘤治疗效果,研究者们针对肿瘤微环境设计出了双重和多重响应性智能纳米药物载体。其中基于酸敏感的双重响应性智能纳米药物载体的研究是最广泛、最常见的一种。在当前的研究中,该智能纳米药物载体已经初步实现了体内长循环、有效地抵达肿瘤细胞、在特定肿瘤微环境下控制药物释放等功效,增加了药物抗肿瘤疗效,有效地减少了药物对机体中正常组织的伤害。但是这类研究仍存在许多问题需要解决,如价格昂贵、载体结构复杂、体内药物传递机理不明确等,使其很难用于临床治疗。这里主要从酸-温度、酸-磁、酸-氧化还原、酸-酶、酸-光和酸-超声几个方面简单介绍了近几年的纳米载体研究进展,为进一步实现纳米药物临床应用奠定基础。     

Receptor-targeted nanocarriers for therapeutic delivery to cancer

Abstract

Efficient and site-specific delivery of therapeutic drugs is a critical challenge in clinical treatment of cancer. Nano-sized carriers such as liposomes, micelles, and polymeric nanoparticles have been investigated for improving bioavailability and pharmacokinetic properties of therapeutics via various mechanisms, for example, the enhanced permeability and retention (EPR) effect. Further improvement can potentially be achieved by conjugation of targeting ligands onto nanocarriers to achieve selective delivery to the tumour cell or the tumour vasculature. Indeed, receptor-targeted nanocarrier delivery has been shown to improve therapeutic responses both in vitro and in vivo. A variety of ligands have been investigated including folate, transferrin, antibodies, peptides and aptamers. Multiple functionalities can be incorporated into the design of nanoparticles, e.g., to enable imaging and triggered intracellular drug release. In this review, we mainly focus on recent advances on the development of targeted nanocarriers and will introduce novel concepts such as multi-targeting and multi-functional nanoparticles.