Targeting colloidal particulates to thoracic lymph nodes

Liu, Jiang; Wong, Ho-Lun; Moselhy, Jim; Bowen, Barry M.; Wu, Xiao Yu; Johnston, Michael

doi:10.1016/j.lungcan.2005.11.006

Cited by 51 publications

(45 citation statements)

References 24 publications

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“…226 Progression of many cancers ͑lung, esophageal, mesothelioma, etc.͒ is seen in the spread of tumor cells to local lymph nodes. 226 The detection and targeted drug delivery to these sites are the steps involved in the therapeutic treatment of cancer.…”

Section: Nanoparticle Translocation To the Lymphatic Systemsmentioning

confidence: 99%

Nanomaterials and nanoparticles: Sources and toxicity

2007

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This review is presented as a common foundation for scientists interested in nanoparticles, their origin, activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of 'nano', while raising awareness of nanomaterials' toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. The reticuloendothelial system in particular actively neutralizes and eliminates foreign matter in the body, including viruses and non-biological particles. Particles originating from human activities have existed for millennia, e.g. smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased anthropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles -"nanoparticles" and expanding the variety of chemical compositions. Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lung, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Examples of toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation, causing abnormal function or cell death. The manipulation of matter at the scale of atoms, "nanotechnology", is creating many new materials with characteristics not always easily predicted from current knowledge. Within the near-limitless diversity of these materials, some happen to be toxic to biological systems, others are relatively benign, while others confer health benefits. Some of these materials have desirable characteristics for industrial applications, as nanostructured materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less lubrication of motors. A rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial develop...

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Section: Nanoparticle Translocation To the Lymphatic Systemsmentioning

confidence: 99%

Nanomaterials and nanoparticles: Sources and toxicity

2007

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“…For ipl administration, Taxol and PLGA-PTX suspension were given into the pleural cavity under isoflurane inhalation anesthesia by means of a transthoracic procedure described previously (8). Taxol was administered without further dilution, whereas PLGA-PTX microspheres were dispersed in injectable water with 0.1% Tween 80.…”

Section: Drug Administrationmentioning

confidence: 99%

“…We have explored the intrapleural (ipl) administration of colloidal particulates as an alternate route to target thoracic lymphatics (8), and developed a biodegradable polymeric microparticulate lymphatic targeting system (9). The system is composed of a proprietary formulation of gelatin sponge containing polylactide-co-glycolide paclitaxel (PTX) microspheres (PLGA-PTX).…”

Section: Introductionmentioning

confidence: 99%

Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer

Liu¹,

Meisner²,

Kwong³

et al. 2009

Cancer Research

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As a means of treating lymphatic metastasis from lung cancer, the pharmacokinetics and therapeutic effects of an intrapleural (ipl) implantable drug delivery system consisting of a gelatin sponge impregnated with polylactide-co-glycolide paclitaxel (PLGA-PTX) microspheres were studied. PLGA-PTX with 7% (w/w) drug loading were incorporated into gelatin matrix. The pharmacokinetics were studied in rats with one of the following regimens: (a) Taxol 8 mg/kg by i.v. injection; (b) Taxol 8 mg/kg ipl; (c) PLGA-PTX (100 mg/kg) ipl; (d) sponge containing PLGA-PTX (100 mg/kg) ipl. PTX concentrations in lymph node and plasma were determined by liquid chromatography mass spectrometry, and the area under the curve (AUC) was calculated. Therapeutic efficacy was assessed in an orthotopic lung cancer model with tumor resection 14 days following tumor implantation. Animals were randomized to ipl placement of PLGA-PTX sponge, placebo sponge, or no treatment. Lymph node metastases were examined at 32 d. The results show that the mediastinal lymph node AUC was significantly higher with ipl.

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“…Moreover, other factors such as size, surface charge, molecular weight, hydrophobicity, types of lipid, and concentration of the emulsifier used have also been observed to influence the uptake and distribution of lipidbased nanoparticles in the lymphatic circulation. 12,39,53,69 …”

Section: In Vitro Modelsmentioning

confidence: 99%

“…A number of natural (dextran and hyaluronic acid) and synthetic (polyhexylcyanoacrylate, polymethylmethacrylate, poly[L-lactic acid], and poly[lacticco-glycolic acid]) polymers have been used as carriers to deliver drugs through the lymphatic system. [47][48][49][50][51][52][53][54] The lymphatic system was previously thought to play a passive role in the spread of disease throughout the body; however, recent findings have opened up a new chapter regarding the role of the lymphatic system in the metastasis of cancer. The discovery of specific markers and growth factors in the lymphatic endothelium, such as vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF-A, the VEGF-D receptor (VEGFR-3), and Prox-1, have provided the opportunity for specific drug targeting to diminish lymphangiogenesis and metastasis in the lymphatic system.…”

Section: Introductionmentioning

confidence: 99%

Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

Khan

Mudassir²,

Mohtar³

et al. 2013

IJN

140

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Abstract:The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipidbased nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.

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Targeting colloidal particulates to thoracic lymph nodes

Cited by 51 publications

References 24 publications

Nanomaterials and nanoparticles: Sources and toxicity

Nanomaterials and nanoparticles: Sources and toxicity

Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer

Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

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