Lipid nanoparticles: tumor-targeting nanocargos for drug and contrast agent delivery (original) (raw)
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ACS Nano, 2011
Nanoparticle applications in medicine have seen a tremendous growth in the past decade. In addition to their drug targeting application and their ability to improve bioavailability of drugs, nanoparticles can be designed to allow their detection with a variety of imaging methodologies. In the current study, we developed a multimodal nanoparticle platform to enable imaging guided therapy, which was evaluated in a colon cancer mouse model. This "theranostic" platform is based on oil-in-water nanoemulsions and carries iron oxide nanocrystals for MRI, the fluorescent dye Cy7 for NIRF imaging, and the hydrophobic glucocorticoid prednisolone acetate valerate (PAV) for therapeutic purposes. Angiogenesis-targeted nanoemulsions functionalized with Rvβ 3 -specific RGD peptides were evaluated, as well. When subcutaneous tumors were palpable, the nanoemulsions were administered at a dose of 30 mg of FeO/kg and 10 mg of PAV/kg. MRI and NIRF imaging showed significant nanoparticle accumulation in the tumors, while tumor growth profiles revealed a potent inhibitory effect in all of the PAV nanoemulsion-treated animals as compared to the ones treated with control nanoemulsions, the free drug, or saline. This study demonstrated that our nanoemulsions, when loaded with PAV, iron oxide nanocrystals, and Cy7, represent a flexible and unique theranostic nanoparticle platform that can be applied for imaging guided therapy of cancer.
Nanoemulsion as Targeted Drug Delivery System for Cancer Therapeutics
Journal of Pharmaceutical Sciences and Pharmacology, 2017
Nanoemulsion serve as an attractive vehicle for the delivery of drugs, nucleic acids as well as imaging agents. Recently nanoemulsions have been extensively used for cancer diagnostics, imaging and therapy, especially due to their favorable properties to efficiently solubilize poorly aqueous soluble drugs, biocompatibility, high stability in vitro and in vivo, and their ability to accumulate in pathological areas with defective vasculatures. Since nanoemulsions are submicron emulsions with the droplet size falling in colloidal dispersion range, they impart the benefit of overcoming the anatomical and physiological barriers associated in drug delivery to the complex diseases such as cancer. Moreover, nanoemulsions can be engineered to carryout multiple functions by surface modification and encapsulation of pharmaceutical ingredients. Surface modification can be done by imparting the surface charge, attaching a targeting ligand, cell penetrating moieties, stimuli-sensitive groups and fluorescent dye, whereas the core can be loaded with drug, contrast agent and imaging agents. Such multifunctionality of nanoemulsion can be tailored to fit the requirement, hence smart nanoemulsions can be prepared. In this review, nanoemulsions of both lipid-based and polymeric micelle have been discussed. Focus has been made on various modifications of nanoemulsions, including those for passive targeting, active targeting, overcoming multi-drug resistance, and multifunctional effect; and are discussed with recent examples from the literature. The multifunctionality of nanoemulsions has further been elaborated for targeting, imaging, and drug and oligonucleotide delivery.
Tumor targeting of functionalized lipid nanoparticles: Assessment by in vivo fluorescence imaging
European Journal of Pharmaceutics and Biopharmaceutics, 2010
Lipid nanoparticles (LNP) coated by a poly(oxyethylene) polymer have been manufactured from low cost and human use-approved materials, by an easy, robust, and up-scalable process. The incorporation in the formulation of maleimide-grafted surfactants allows the functionalization of the lipid cargos by targeting ligands such as the cRGD peptide binding to a v b 3 integrin, a well-known angiogenesis biomarker. LNP are able to encapsulate efficiently lipophilic molecules such as a fluorescent dye, allowing their in vivo tracking using fluorescence imaging. In vitro study on HEK293(b3) cells over-expressing the a v b 3 integrins demonstrates the functionalization, specific targeting, and internalization of cRGD-functionalized LNP in comparison with LNP-cRAD or LNP-OH used as negative controls. Following their intravenous injection in Nude mice, LNP-cRGD can accumulate actively in slow-growing HEK293(b3) cancer xenografts, leading to tumor over skin fluorescence ratio of 1.53 ± 0.07 (n = 3) 24 h after injection. In another fast-growing tumor model (TS/A-pc), tumor over skin fluorescence ratio is improved (2.60 ± 0.48, n = 3), but specificity between the different LNP functionalizations is no more observed. The different results obtained for the two tumor models are discussed in terms of active cRGD targeting and/or passive nanoparticle accumulation due to the Enhanced Permeability and Retention effect.
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Based on oil-in-water template emulsion, lipid nanoemulsion has been developing with monitoring both the lipid-shell and lipid-core composition imparting outstanding long-term stability of nanoparticles. Taking advantage of its colloidal behavior and high tolerability, we modulated the surface droplet to tailor make relevant nanocarriers and also transport various molecules such as large drugs, biomacromolecules. Cationic and anionic nanoparticles were prepared by incorporation of either hydrophobic-tailed polysaccharides or cationic lipids within the shell lipids. Such cationic formulations are suitable for the complexation of nucleic acids such as DNA or RNA. Moreover, large biomacromolecules, such as proteins, peptides or antibodies are chemically grafted on nanoparticle surface via bioconjugation techniques using “home-made” PEGylated surfactants. Also, the fine-tuning of shell of lipid nanoemulsion offers great opportunity to adress new applications in targeted delivery field (...
Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment
Nanomaterials, 2019
Many therapeutically active molecules are non-soluble in aqueous systems, chemically and biologically fragile or present severe side effects. Lipid-based nanoparticle (LBNP) systems represent one of the most promising colloidal carriers for bioactive organic molecules. Their current application in oncology has revolutionized cancer treatment by improving the antitumor activity of several chemotherapeutic agents. LBNPs advantages include high temporal and thermal stability, high loading capacity, ease of preparation, low production costs, and large-scale industrial production since they can be prepared from natural sources. Moreover, the association of chemotherapeutic agents with lipid nanoparticles reduces active therapeutic dose and toxicity, decreases drug resistance and increases drug levels in tumor tissue by decreasing them in healthy tissue. LBNPs have been extensively assayed in in vitro cancer therapy but also in vivo, with promising results in some clinical trials. This re...
LIPID BASED NANOPARTICLES IN CANCER THERAPY
Indo American Journal of Pharmaceutical Research, 2023
Investigators were continuously creating novel nanotechnologies to address unmet requirements throughout the administration of therapeutic medicines & imaging agents for cancer treatment & diagnostics, appropriately. LNPs (Lipid nanoparticles) are legitimate particulates (approx. 100 nm in size) gathered from various lipid as well as other biochemical compounds which overall functionality to resolve biological barriers (bioba rriers), allowing LNPs to selectively collect somewhere outside of disease-target cells again for responsive therapeutics. Most pharmaceutically important compounds were insoluble throughout water solutions, were chemical & physiologically unstable, or have toxicities. Among the most potential drug carrier for bioactive organic compounds is LBNPs (Lipid based nanoparticles) technologies. Its present use in chemotherapy has transformed treatment for cancer by increasing the antitumor effect of a number of chemotherapeutics. Because they may be created using naturally occurring sources, LBNPs have great temporal and thermal stability, maximum load potential, simplicity of preparations, cheap manufacturing costs, & big manufacturing output. Furthermore, combining chemotherapeutic drugs with LNPs reduces active therapeutic dosage and toxicities, lowers treatment resistance, & raises drug concentration in tumour cells while reducing concentrations in normal tissue. LBNPs were widely studied in cancer treatment, both in vitro and in vivo, with encouraging outcomes in certain clinical trials. This study provides an overview of the many types of LBNPs which have been created in latest years and their applications and contributions in different types of cancers.
Lipid-based nanoparticles for treatment of cancer
Heliyon
Investigators were continuously creating novel nanotechnologies to address unmet requirements throughout the administration of therapeutic medicines & imaging agents for cancer treatment & diagnostics, appropriately. LNPs(Lipid nanoparticles) are legitimate particulates (approx. 100 nm in size) gathered from various lipid as well as other biochemical compounds which overall functionality to resolve biological barriers (biobarriers), allowing LNPs to selectively collect somewhere outside of disease-target cells again for responsive therapeutics. Most pharmaceutically important compounds were insoluble throughout water solutions, were chemical & physiologically unstable, or have toxicities. Among the most potential drug carrier for bioactive organic compounds is LBNPs (Lipid based nanoparticles) technologies. Its present use in chemotherapy have transformed treatment for cancer by increasing the antitumor effect of a number of chemotherapeutics. Because they may be created using naturally occurring sources, LBNPs have great temporal and thermal stability, maximum load potential, simplicity of preparations, cheap manufacturing costs, & big manufacturing output. Furthermore, combining chemotherapeutic drugs with LNPs reduces active therapeutic dosage and toxicities, lowers treatment resistance, & raises drug concentration in tumour cells while reducing concentrations in normal tissue. LBNPs were widely studied in cancer treatment, both in vitro and in vivo, with encouraging outcomes in certain clinical trials. This study provides an overview of the many types of LBNPs which have been created in latest years and their applications and contributions in different types of cancers. ☆ This article is a part of the "Lipid-Based Nanoparticles in Diagnosis and Treatment" Special issue.
Nanostructured Lipid Carriers: A Novel Platform for Chemotherapeutics
Cancer is a disease manifested as abnormal cells division without control. If it is not detected and cured very timely, it can invade other healthy tissues resulting in metastasis. Chemotherapy is the first line treatment for cancer, but due to lack of specificity of most of the anticancer drugs, is associated with side effects that affect the quality of life. Nanostructured lipid carriers (NLC) are one of the promising nano-carriers for the development of effective targeted therapies for cancer chemothera-peutics. These bio-compatible and/or biodegradable lipids based nanoparticles are composed of solid and liquid lipids as a core matrix dispersed in surfactant solution. NLC improve the aqueous solubility of most of the hydrophobic cancer therapeutics. Their surface modification can be used for overcoming drug resistance in cancer chemotherapy, to achieve site specific targeting for better efficacy and reduced dose related toxicity. The present review is an attempt to contemplate their pharmaceutical, biopharmaceutical aspects and application in cell targeting, gene delivery and in theranostics.
Nanomedicine for Cancer: Lipid-Based Nanostructures for Drug Delivery and Monitoring
Accounts of Chemical Research, 2011
R ecent advances in nanotechnology, materials science, and biotechnology have led to innovations in the field of nanomedicine. Improvements in the diagnosis and treatment of cancer are urgently needed, and it may now be possible to achieve marked improvements in both of these areas using nanomedicine. Lipid-coated nanoparticles containing diagnostic or therapeutic agents have been developed and studied for biomedical applications and provide a nanomedicine strategy with great potential. Lipid nanoparticles have cationic headgroups on their surfaces that bind anionic nucleic acids and contain hydrophobic drugs at the lipid membrane and hydrophilic drugs inside the hollow space in the interior. Moreover, researchers can design nanoparticles to work in combination with external stimuli such as magnetic field, light, and ionizing radiation, which adds further utility in biomedical applications. In this Account, we review several examples of lipid-based nanoparticles and describe their potential for cancer treatment and diagnosis. (1) The development of a lipid-based nanoparticle that included a promoterÀenhancer and transcriptional activator greatly improved gene therapy. (2) The addition of a radiosensitive promoter to lipid nanoparticles was sufficient to confer radioisotope-activated expression of the genes delivered by the nanoparticles. (3) We successfully tailored lipid nanoparticle composition to increase gene transduction in scirrhous gastric cancer cells. (4) When lipophilic photosensitizing molecules were incorporated into lipid nanoparticles, those particles showed an increased photodynamic cytotoxic effect on the target cancer. (5) Coating an Fe 3 O 4 nanocrystal with lipids proved to be an efficient strategy for magnetically guided gene-silencing in tumor tissues. (6) An Fe 16 N 2 /lipid nanocomposite displayed effective magnetism and gene delivery in cancer cells. (7) Lipid-coated magnetic hollow capsules carried aqueous anticancer drugs and delivered them in response to a magnetic field. (8) Fluorescent lipid-coated and antibody-conjugated magnetic nanoparticles detected cancer-associated antigen in a microfluidic channel. We believe that the continuing development of lipid-based nanomedicine will lead to the sensitive minimally invasive treatment of cancer. Moreover, the fusion of different scientific fields is accelerating these developments, and we expect these interdisciplinary efforts to have considerable ripple effects on various fields of research.
Lipid nanoparticle mediated drug delivery for safer cancer treatment
2009
COMO REFERENCIAR ESTE ARTIGO: DoktoroVoVA, slavomira; lopes, carla martins ; souto, eliana b.-lipid nanoparticle mediated drug delivery for safer cancer treatment: example of paclitaxel. Revista da Faculdade de Ciências da Saúde. porto : edições universidade Fernando pessoa. issn 1646-0480. 6 (2009) 84-93. 85 RESUMO os vectores coloidais de natureza lipídica têm atraído particular atenção para o desenvolvimento de terapias mais seguras e eficazes aplicadas a várias doenças. As vantagens da utilização das nanopartículas lipídicas são exemplificadas utilizando o paclitaxel, um anticancerígeno particularmente interessante para o desenvolvimento de novas formas farmacêuticas mais adequadas para o tratamento do cancro. De facto, este fármaco apresenta problemas de insolubilidade aquosa e sérios efeitos secundários concomitantes à administração da forma farmacêutica convencional (taxol). este artigo apresenta uma revisão das razões para a reformulação do paclitaxel e sumariza as vantagens de novas formas farmacêuticas contendo nanopartículas lipídicas para a administração deste anticancerígeno. PALAVRAS-ChAVE nanopartículas de lípidos sólidos, vectores lipídicos nanoestruturados, nanopartículas lipídicas, paclitaxel, tratamento do cancro ABSTRACT colloidal carriers composed of lipids attract much attention in the development of safer and more effective therapy of various diseases. the advantages of lipid-based nanoparticles are illustrated on the example of paclitaxel, a challenging chemotherapeutic drug for the development of a novel and more suitable dosage form for cancer treatment. paclitaxel is known for its water insolubility and serious side effects when administered by its conventional formulation (taxol). this paper reviews the reasons of further re-formulation of paclitaxel and summarizes the achievements of lipid nanoparticle-based formulations of this drug.