State-of-the-art in design rules for drug delivery platforms: Lessons learned from FDA-approved nanomedicines

Dawidczyk, Charlene M.; Kim, Chloe; Park, Jea Ho; Russell, Luisa M.; Lee, Kwan H.; Pomper, Martin G.; Searson, Peter C.

doi:10.1016/j.jconrel.2014.05.036

Cited by 461 publications

(343 citation statements)

References 100 publications

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“…According to the observations in [20], we estimate r por = 1.0µm, a value consistent with the multiple fenestrations that characterize a malignant vascular network. The molecule radius can be estimated from the Stokes-Einstein equation: (33) where k B T is the Boltzmann thermal energy. We find r vin = 2.98 × 10 −8 m and r dox = 1.13 × 10 −9 m for Vinblastine and Doxorubicin radii, respectively.…”

Section: Physiological Parametersmentioning

confidence: 99%

The role of the microvascular network structure on diffusion and consumption of anticancer drugs

Mascheroni

Penta

2017

Numer Methods Biomed Eng

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SUMMARYWe investigate the impact of the tumor microvascular geometry on transport of drugs in solid tumors, in particular focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations which is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells. The coefficients are then injected into the macroscale equations, which are solved for an isolated, vascularized spherical tumor. We consider the effect of vascular tortuosity on the transport of anti-cancer molecules, focusing on the Vinblastine and Doxorubicin dynamics, which can be considered a tracer and a highly interacting molecule, respectively. The computational model is able to quantify the performance of the treatment through the analysis of the interstitial drug concentration and the quantity of drug metabolized in the tumor. Our results show that both drug advection and diffusion are dramatically impaired by increasing geometrical complexity of the microvasculature, leading to non-optimal absorption and delivery of therapeutic agents. However, this effect apparently has a minor role whenever the dynamics are mostly driven by metabolic reactions in the tumor interstitium, i.e. for highly interacting molecules. In the latter case, anti-cancer therapies that aim at regularizing the microvasculature might not play a major role and different strategies are to be developed.

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Section: Physiological Parametersmentioning

confidence: 99%

The role of the microvascular network structure on diffusion and consumption of anticancer drugs

Mascheroni

Penta

2017

Numer Methods Biomed Eng

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“…Despite numerous cancer studies and the development of various anti-cancer therapeutic agents, cancer remains dangerous. Anti-cancer therapeutic agents are chemically or biologically produced, and their effects are well defined (3)(4)(5)(6)(7). However, treatments continue to be associated with adverse effects and the majority of patients have an aversion to them (8).…”

Section: Introductionmentioning

confidence: 99%

Barley grass extract causes apoptosis of cancer cells by increasing intracellular reactive oxygen species production

Woo

Kwon

et al. 2017

Biomedical Reports

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Abstract. Cancer remains a leading cause of mortality worldwide, therefore food products are being investigated for potential prevention or treatment strategies. The ingredient, barley grass extract (Hordeum vulgare L.; Bex) is used to prevent or ameliorate various types of disease. In cancer, Bex has been revealed to inhibit tumor growth. However, its effect on cancer cells is yet to be clearly defined. In the present study, the effect of Bex on cancer cell growth was investigated. Bex inhibited the viabilities of breast and prostate cancer cells according to the results of MTT assays. Accordingly, Bex caused apoptosis, which was confirmed by Annexin V staining and western blot analysis for poly (ADP-ribose) polymerase and caspases. Furthermore, Bex increased the intracellular levels of reactive oxygen species (ROS), and N-acetyl-L-cystein blocked Bex-induced apoptosis. Therefore, the study demonstrated that Bex causes apoptosis of breast and prostate cancer cells by increasing intracellular ROS levels. IntroductionCancer is one of the leading causes of mortality worldwide (1,2). Despite numerous cancer studies and the development of various anti-cancer therapeutic agents, cancer remains dangerous. Anti-cancer therapeutic agents are chemically or biologically produced, and their effects are well defined (3-7). However, treatments continue to be associated with adverse effects and the majority of patients have an aversion to them (8).Herbal products have long been used to prevent or treat diseases, including cancer (9-12). Furthermore, certain anti-cancer therapeutic agents that are chemically produced originate from herbal products and their chemical characteristics are modified (7,(12)(13)(14). Typically, patients prefer to take herbal products (15-18); herbal products have historically been used as traditional medicines, such as traditional Chinese and Korean medicines, Kampo medicines and Ayurvedic medicine (13,14,19). Certain herbal products were demonstrated to treat cancer and/or reduce the side effects of cancer treatment (13,(15)(16)(17)(19)(20)(21). Therefore, herbal products are considered to be promising for cancer prevention and treatment.Barley grass extract (Hordeum vulgare L.; Bex) has long been used as a food product. Its biological effects have also been addressed by various in vitro and in vivo studies, although evidence there is limited evidence of the efficacy of Bex against specific conditions (22). The effect of Bex on the immune system was revealed in in vitro and in vivo experimental sets (23-25). Accordingly, Bex inhibited atopic dermatitis in NC/Nga mice by altering the expression levels of cytokines (26). Similarly, Bex repressed lipopolysaccharide-induced inflammation (27). Furthermore, its effect in type 2 diabetes was revealed in a genetically engineered mouse model and patients (28,29). Therefore, the effects of Bex on particular diseases have been demonstrated at least in experimental systems. A previous study revealed that Bex caused apoptosis of leukemia and lymphoma cell lines...

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“…[13][14][15] Several wellstudied materials have been developed into clinically available formulations, such as Abraxane ® and Doxil ® . 16,17 At the same time, a category of self-assembling peptides as novel nanomaterials has emerged in the past decade with advanced properties in 18,19 Based on their chemical structures, selfassembling peptides could form different nanostructures including nanoparticles, nanotubes, and nanofibers, which are also potential carriers for drug delivery. [20][21][22][23][24][25][26] It has been demonstrated that nanostructures with a high aspect ratio are advantageous as drug carriers; 27,28 however, on the other hand, their drug loading capacity (LC) is usually very low, 24,29 which has hampered the development of a drug delivery system based on these nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs

Chen¹,

Tang²,

Zhang³

et al. 2015

IJN

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Background Finding a suitable delivery system to improve the water solubility of hydrophobic drugs is a critical challenge in the development of effective formulations. In this study, we used A 6 K, a self-assembling surfactant-like peptide, as a carrier to encapsulate and deliver hydrophobic pyrene. Methods Pyrene was mixed with A 6 K by magnetic stirring to form a suspension. Confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, atomic force microscopy, fluorescence, and cell uptake measurements were carried out to study the features and stability of the nanostructures, the state and content of pyrene, as well as the pyrene release profile. Results The suspension formed contained pyrene monomers trapped in the hydrophobic cores of the micellar nanofibers formed by A 6 K, as well as nanosized pyrene crystals wrapped up and stabilized by the nanofibers. The two different encapsulation methods greatly increased the concentration of pyrene in the suspension, and formation of pyrene crystals wrapped up by A 6 K nanofibers might be the major contributor to this effect. Furthermore, the suspension system could readily release and transfer pyrene into living cells. Conclusion A 6 K could be further exploited as a promising delivery system for hydrophobic drugs.

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State-of-the-art in design rules for drug delivery platforms: Lessons learned from FDA-approved nanomedicines

Cited by 461 publications

References 100 publications

The role of the microvascular network structure on diffusion and consumption of anticancer drugs

The role of the microvascular network structure on diffusion and consumption of anticancer drugs

Barley grass extract causes apoptosis of cancer cells by increasing intracellular reactive oxygen species production

Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs

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