다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

In the golden age of pharmaceutical nanocarriers, we are witnessing a maturation stage of the original concepts and ideas. There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. In this context, lipid nanoparticles have gained ground, since they are generally regarded as non-toxic, biocompatible and easy-to-produce formulations. Pharmaceutical applications of lipid nanocarriers are a burgeoning field for the transport and delivery of a diversity of therapeutic agents, from biotechnological products to small drug molecules. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic preformulation studies. The main applications, as well as the advantages that this type of nanovehicles offers in certain therapeutic scenarios are discussed. Next, pharmacokinetic aspects are described, such as routes of administration, absorption after oral administration, distribution in the organism (including brain penetration) and elimination processes. Safety and toxicity issues are also addressed. Our work presents an original point of view, addressing the biopharmaceutical aspects of these nanovehicles by means of descriptive statistics of the state-of-the-art of solid lipid nanoparticles research. All the presented results, trends, graphs and discussions are based in a systematic (and reproducible) bibliographic search that considered only original papers in the subject, covering a 7 years range (2013-today), a period that accounts for more than 60% of the total number of publications in the topic in the main bibliographic databases and search engines. Focus was placed on the therapeutic fields of application, absorption and distribution processes and current efforts for the translation into the clinical practice of lipid-based nanoparticles. For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials.

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Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects

INTRODUCTION: 
Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. 

METHODS: 
Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. 

RESULTS: 
A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). 

CONCLUSION: 
PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

Threatening cancer with nanoparticle aided combination oncotherapy

The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

https://www.mdpi.com/1999-4923/12/3/233/pdf

Gene Therapy in Cancer Treatment: Why Go Nano?

A majority of drug discovery programs lead to the development of drug candidates that are highly potent and poorly water soluble. Poor drug solubility offers numerous challenges such as reduced bioavailability on oral administration, a lack of equivalence in fed and fasted state, and abandonment of drug molecule in the early stage of drug development. Many strategies, such as micronization, prodrug development, complexation, etc. have been employed for overcoming the drawbacks of poor solubility and subsequently reduced bioavailability of drug. Among these approaches, development of colloidal drug carrier systems have attracted tremendous interest among the scientific community in the last two decades. Lipid nanoparticulate systems (LNS) are emerging as ideal carriers for imparting improved bioavailability of drugs along with controlled release property. Lipid nanoparticulate systems remain a carrier of choice, as they have been claimed to combine all the advantages and avoid disadvantages of other colloidal carriers. Various type of LNSs have been employed for delivery of active molecules viz. solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), drug–lipid conjugates, lipid nanocapsules, liposomes, layersomes and lipid–polymer nanohybrids. These carrier systems are mainly composed of physiologically biocompatible and biodegradable lipid materials, surfactants, and cosurfactants that are generally regarded as safe and accepted by regulatory authorities. This book chapter will mainly focus on two major types of LNS: SLNs and NLCs. The chapter will comprehensively describe the advantages offered by SLNs/NLCs, their structure, type and composition of SLNs/NLCs, methods employed for formulating them, characterization, as well as safety and toxicological aspects of SLNs/NLCs. Furthermore, applications by different routes of administration will also be discussed.

Lipid nanoparticulate systems: Modern versatile drug carriers

The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, w...

Surface engineered lipid nanoparticle-mediated site-specific drug delivery system for the treatment of inflammatory bowel disease.

Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is the leading cancer killer in both men and women in every Ethnic Group. A major problem associated wi...

Fabrication, optimization, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers for improved anticancer activity

Lung cancer is one of the leading cancer killer in both men and women worldwide. Toxicity of anticancer drugs towards normal cells is one of the major concern impeding the effective chemotherapy. Artemether (ART), an anti-malarial agent, revealed cytotoxic effect on tumor cells by down-regulating the expression of matrix metalloproteinase (MMP)−9, hypoxia-inducible factor (HIF)−1a, VEGF and other related proteins. The present investigation demonstrates development of ART loaded solid lipid nanoparticles (ART-SLNs) for the treatment of lung cancer. A 23 full factorial design was applied to optimize ART-SLNs systematically. Concentration of drug, surfactant concentration and homogenization cycles were selected as an independent variables, and % drug loading (%DL), % entrapment efficiency (%EE) and particle size were selected as dependent variables. The mean diameter of optimized ART-SLNs was found to be 419 ± 09 nm, with %EE of 78.66 ± 1.93%, and %DL of 9.17 ± 0.11%. The in vitro dissolution studies revealed sustained drug release profile, revealing best fit with Korsmeyer-Peppas model. Further, the in vitro lipolysis study confirmed that ART-SLNs stabilized using MPEG2000-DSPE, exhibited anti-lipolytic effect. The stability (accelerated) studies does not showed any significant change in characteristics of developed ART-SLNs.

https://iopscience.iop.org/article/10.1088/2053-1591/aaf8a3/pdf

Shruti Rawal

Papers

Threatening cancer with nanoparticle aided combination oncotherapy

Lipid nanoparticulate systems: Modern versatile drug carriers

Surface engineered lipid nanoparticle-mediated site-specific drug delivery system for the treatment of inflammatory bowel disease.

Fabrication, optimization, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers for improved anticancer activity

Fabrication, characterization and optimization of artemether loaded PEGylated solid lipid nanoparticles for the treatment of lung cancer