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Understanding the Interaction of Nanoparticles at the Cellular Interface
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Cancer cell is quite different from normal cells in many ways; therefore, the interaction of NPs with cancer cells would encourage a new area of research. The selective accumulation of therapeutic nanomaterials of a particular size at a tumor site is based on the controversial enhanced permeability and retention effect (EPR). The leaky vasculature and tumor microenvironment, production of an abnormal amount of vascular growth factors, and vascular permeability enhancing elements (such as bradykinin, nitric oxide, and prostaglandins) are significant factors for controlling the EPR effect [74]. It has been found that less than a 2-fold increase of nanomedicine in tumor site compared to normal organ is sufficient to cure cancer completely [75]. There are numerous methods for increasing the concentration of NPs at a tumor site. Remote controlled and stimuli-responsive smart NPs are good candidates for therapeutic strategies.
Drug Delivery
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Gudrun Fleischhack, Martin Garnett, Kévin Beccaria
For macromolecules and nanoparticles uptake into cells cannot occur by diffusion and it is usually affected by various endocytic mechanisms which may or may not be receptor-mediated. In some of the early literature on drug delivery to tumors the accumulation of macromolecules into tumors and particularly within the lysosomal compartment of cells was said to be enhanced compared to that in normal tissues and led to the promotion of the concept by De Duve et al. of lysosomotropic delivery to cells.8 This early theory was based on in vivo work, which was not repeatable in vitro.9 However, more recent work by one of us (M.G.) has shown that nanoparticles are endocytosed into tumor cells more effectively than normal brain cells when grown in three-dimensional tissue culture but not in two-dimensional (2D) tissue culture,10,11 thus giving us an in vitro model for these in vivo observations. This work is of significance not only because it suggests that it would further enhance the effectiveness of macromolecular and nanoparticulate delivery systems taking advantage of the enhanced permeability and retention effect, but may also enhance uptake of drugs specifically into tumor cells. This finding offers the prospect of delivery systems which show specificity between normal and tumor cells at the periphery of a tumor, without the disadvantages of the binding-site effect seen in the more complex targeted formulations.
Nanotechnology: Regulatory Perspective for Drug Development in Cancer Therapeutics
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Another early nanomedicine, liposomal encapsulated doxorubicin (Doxil®), is regulated by the FDA and has been available in the clinic for treatment of various cancers since 1995. Drug incorporation inside the hydrophilic core or within the hydrophobic phospholipid bilayer coat of liposomes, has been shown to improve drug solubility, enhance drug transfer into cells and tissues, facilitate organ avoidance, and modify drug release profiles, minimizing toxicity.91 The liposomal formulation of the popular anthracyline, doxorubicin, which is commonly used to treat metastatic breast and ovarian cancer, is reported to have diminished cardiotoxicity and enhanced therapeutic efficacy compared to the free form of the drug.15–17 This increased efficacy is most likely due to the passive targeting of solid tumors through the enhanced permeability and retention effect inherent to tumor vasculature and aberrant tumor morphology.17 The approximate diameter of the doxorubicin–liposomal product is reported to be 100 nm, near the size limits described in the FDA definition of a nanomedicine.
Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation
Published in Expert Opinion on Drug Delivery, 2022
Alaa Ibrahim, Sara A. Abdel Gaber, Mohamed Fawzi Kabil, Omar A.H. Ahmed-Farid, Anna K.H. Hirsch, Ibrahim M. El-Sherbiny, Maha Nasr
Nanotechnology as an emerging technique can play a dual role in the treatment of brain cancer; since nanoparticles are able to cross the blood–brain barrier and hence can be used in treatment of brain-related diseases. They have played an important role so far in optimizing the therapeutic effect of drugs in the treatment of cancer, owing to their enhanced permeability and retention effect, and their enhanced internalization within cancer cells [4–7]. In addition to the use of nanocarriers, the choice of route of drug administration is of equal importance, since it greatly influences the pharmacokinetics of drugs and the extent of their action [8]. Among the promising routes of drug administration which can ensure high concentrations of drugs in the brain besides the intravenous route is the intranasal route, which provides a shunt to the brain via the olfactory region [9].
Investigation of dimyristoyl phosphatidyl glycerol and cholesterol based nanocochleates as a potential oral delivery carrier for methotrexate
Published in Journal of Liposome Research, 2022
Bothiraja Chellampillai, Sneha Kashid, Atmaram Pawar, Ashwin Mali
The MTX concentration was subsequently assayed in major organs such as liver, lungs, kidney, heart, spleen and brain at 8h after oral administration of a dose of 10mg/kg of free MTX, MTX-NLs and MTX-NCs. As shown in Figure 9, the MTX-NCs showed 3.2, 1.7, 1.8 and 3.1 fold lower distributions in heart, lung, spleen and brain with 2.1 fold higher distribution in the kidney as compared free MTX and a similar amount of free MTX and MTX-NCs in the liver due to endocytosis process which could be advantages to treat liver and kidney cancer. It can be noticed that the drug was distributed mainly in the liver where it was metabolised and in the kidneys, which were responsible for elimination. Cancer cells are rapidly dividing cells, where MTX can accumulate easily as a consequence of their requirement for high amounts of folates for replication. Further, NLs & NCs administration and extravasations of drug-loaded particles towards breast cancer and enhanced permeability and retention effect are probably favoured by leaky vascular architecture in neoplastic tissue.
Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis
Published in Journal of Liposome Research, 2021
Xue-Tao Li, Ming Jing, Fu-Yi Cai, Xue-Min Yao, Liang Kong, Xiao-Bo Wang
In order to observe the real-time distribution of the varying liposomal formulations in vivo, a non-invasive optical imaging system was used to capture real-time images of gastric tumour-bearing mice. Results showed that free DiR had no fluorescent signal in tumour tissues. On the contrary, R8GD-modified DiR plus tetrandrine liposomes exhibited the strong fluorescent signals in tumour sites (Figure 7). The in vivo image results further verified that the modification of R8GD could enhance the biodistribution of the targeting liposomes in tumour sites. The pharmacodynamics of the varying liposomal formulations was carried out from different aspects. Results showed that R8GD-modified epirubicin plus tetrandrine liposomes exhibited the strongest antitumor effects (Figure 8). The enhanced antitumour efficiency could be explained by the following reasons: (i) the enhanced permeability and retention effect (EPR) was fully utilised for passive targeting to tumour tissues (Balo et al.2019, Cheng et al.2020); (ii) the modification of R8GD on the liposomal surface enhanced the intracellular uptake via membrane-penetrating and ανβ3 receptor-mediated endocytosis; (iii) the addition of tetrandrine obviously inhibited tumour metastasis via blocking tumour invasion and destroying energy supply; (iv) the lipid material of DSPE-PEG2000 enhanced the stability of the targeting liposomes in blood and prolonged the circulation time in vivo for the more accumulation in tumour tissues.