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A Review on Targeting Nanoparticles for Breast Cancer.
Alqaraghuli, HGJ, Kashanian, S, Rafipour, R
Current pharmaceutical biotechnology. 2019;(13):1087-1107
Abstract
Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.
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2.
Tailoring the Chemical Modification of Chitosan Hydrogels to Fine-Tune the Release of a Synergistic Combination of Chemotherapeutics.
Schneible, JD, Singhal, A, Lilova, RL, Hall, CK, Grafmüller, A, Menegatti, S
Biomacromolecules. 2019;(8):3126-3141
Abstract
Combination chemotherapy with a defined ratio and sequence of drug release is a clinically established and effective route to treat advanced solid tumors. In this context, a growing body of literature demonstrates the potential of hydrogels constructed with chemically modified polysaccharides as depots for controlled release of chemotherapeutics. Identifying the appropriate modification in terms of physicochemical properties of the functional group and its degree of substitution (χ) to achieve the desired release profile for multiple drugs is, however, a complex multivariate problem. To address this issue, we have developed a computational toolbox that models the migration of a drug pair through a hydrated network of polysaccharide chains modified with hydrophobic moieties. In this study, we chose doxorubicin (DOX) and Gemcitabine (GEM) as model drugs, as their synergistic effect against breast cancer has been thoroughly investigated, and chitosan as the model polymer. Our model describes how the modification of chitosan chains with acetyl, butanoyl, and heptanoyl moieties at different values χ governs both the structure of the hydrogel network and drug migration through it. Our experimental data confirm the in silico predictions for both single- and dual-drug release and, most notably, the counterintuitive inversion of release vs χ that occurs when switching from a single- to a dual-drug system. Consensus between predicted and experimental data indicates that acetyl modifications (χ = 32-42%) and butanoyl modifications (χ = 19-24%) provide synergistic GEM/DOX release molar ratios (i.e., 5-10). Collectively, these results demonstrate the potential of this model in guiding the design of chemotherapeutic hydrogels to combat cancer.
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3.
The Potential of Fucose-Containing Sulfated Polysaccharides As Scaffolds for Biomedical Applications.
Nunes, C, Coimbra, MA
Current medicinal chemistry. 2019;(35):6399-6411
Abstract
Marine environments have a high quantity and diversity of sulfated polysaccharides. In coastal regions brown algae are the most abundant biomass producers and their cell walls have fucosecontaining sulfated polysaccharides (FCSP), known as fucans and/or fucoidans. These sulfated compounds have been widely researched for their biomedical properties, namely the immunomodulatory, haemostasis, pathogen inhibition, anti-inflammatory capacity, and antitumoral. These activities are probably due to their ability to mimic the carbohydrate moieties of mammalian glycosaminoglycans. Therefore, the FCSP are interesting compounds for application in health-related subjects, mainly for developing scaffolds for delivery systems or tissue regeneration. FCSP showed potential for these applications also due to their ability to form stable 3D structures with other polymers able to entrap therapeutic agents or cell and growth factors, besides their biocompatibility and biodegradability. However, for the clinical use of these biopolymers well-defined reproducible molecules are required in order to accurately establish relationships between structural features and human health applications.
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4.
Recent Strategies in Resveratrol Delivery Systems.
Machado, ND, Fernández, MA, Díaz, DD
ChemPlusChem. 2019;(7):951-973
Abstract
Resveratrol, a natural polyphenolic stilbenoid widely found in grapes and wines, displays beneficial properties such as cardio-protective, antioxidant and anti-inflammatory activities. Trans-resveratrol (RSV) is the most bioactive and more abundant stereoisomer found in nature. Despite the positive properties of RSV, there are various factors that limit its effectiveness, including low aqueous solubility, low oral bioavailability and chemical instability. During the last years, an increasing number of strategies such as nano and micro encapsulation have been developed in order to overcome these limitations and enhance the use of RSV in nutritional and pharmaceutical applications. This Review summarizes the advances and main properties of several RSV carriers and delivery systems reported during the last 5 years.
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5.
Solid dispersion technology as a strategy to improve the bioavailability of poorly soluble drugs.
Cid, AG, Simonazzi, A, Palma, SD, Bermúdez, JM
Therapeutic delivery. 2019;(6):363-382
Abstract
Over the last half-century, solid dispersions (SDs) have been intensively investigated as a strategy to improve drugs solubility and dissolution rate, enhancing oral bioavailability. In this review, an overview of the state of the art of SDs technology is presented, focusing on their classification, the main preparation methods, the limitations associated with their instability, and the marketed products. To fully take advantage of SDs potential, an improvement in their physical stability and the ability to prolong the supersaturation of the drug in gastrointestinal fluids is required, as well as a better scientific understanding of scale-up for defining a robust manufacturing process. Taking these limitations into account will contribute to increase the number of marketed pharmaceutical products based on SD technology.
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6.
Kinetic investigation of a controlled drug delivery system based on alginate scaffold with embedded voids.
Bhasarkar, J, Bal, D
Journal of applied biomaterials & functional materials. 2019;(2):2280800018817462
Abstract
Alginate scaffold has been used widely for controlled release applications because of its ability to provide three-dimensional supports for formation of a gel matrix. Alginate gel scaffolds for drug delivery matrices were prepared using a fluidic device. N2 gas was used in the fluidic device to generate bubbles in the gel layer. The hydrogel matrices with induced voids were compared with hydrogel matrices without voids. This study attempted to identify the release mechanism of vitamin B12 from the two types of prepared scaffolds, and the data were fitted with different release kinetic models. The results revealed that the alginate scaffold exhibited a controlled release profile and that the corresponding release mechanism followed a first-order kinetic model. Hydrogel scaffolds fabricated with biocompatible polymers using fluidic methods could be promising for controlled drug delivery systems.
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7.
What potential do magnetic iron oxide nanoparticles have for the treatment of rheumatoid arthritis?
Wu, L, Shen, S
Nanomedicine (London, England). 2019;(8):927-930
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8.
Strategies in the design of endosomolytic agents for facilitating endosomal escape in nanoparticles.
Ahmad, A, Khan, JM, Haque, S
Biochimie. 2019;:61-75
Abstract
Nanoparticles (NPs) are one of the leading and promising technologies for gene and drug delivery. However, despite continuous advancements in the delivery of NPs, endosomal escape remains a major issue and a matter of grave concern for developing an efficient and targeted delivery system for therapeutic applications. Most of NPs generally follow endocytic pathway for internalization into the cells. Following the internalization process, NPs must escape into the cell cytoplasm for evading degradation by hydrolytic enzymes present in the lysosomes. Various types of lipids have been used in the past viz. fusogenic lipid dioleoylphosphatidylethanolamine (DOPE), pH-sensitive lipids, cationic lipid and multiple charges containing lipid to escape from endosomes. Recently, several novel polymers, pH-sensitive peptides, proteins and many others endosomolytic agents have been identified and developed for incorporating into gene and drug delivery system to facilitate endosomal escape. In this review, endosomal escape mechanisms of different types of NPs have been discussed in detail and compared with endosomal escape mechanisms of viruses and other synthetic gene delivery systems to escape from endosomes. Also, the designing of endosomolytic agents to facilitate endosomal escape based on different approaches and strategies is explored. Moreover, this review article highlights the recent advancements in the development of NPs equipped with endosomolytic agents including its future directions and applications in the field of nanomedicine.
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9.
Understanding drug distribution and release in ophthalmic emulsions through quantitative evaluation of formulation-associated variables.
Dong, Y, Hengst, L, Hunt, R, Patel, D, Vo, A, Choi, S, Ashraf, M, Cruz, CN, Xu, X
Journal of controlled release : official journal of the Controlled Release Society. 2019;:96-105
Abstract
Establishing bioequivalence (BE) of ophthalmic emulsions in the absence of in vivo data is challenging. In these emulsions, drug release is a complex process due to drug distribution among various phases which are difficult to characterize. The objective of this study is to investigate the process of drug distribution and mechanism of drug release in the context of formulation-associated variables. A previously reported kinetic method for determining drug partitioning was used to quantitatively evaluate the drug distribution within a simplified biphasic (emulsion) system employing cyclosporine and difluprednate as model drugs. The impacts of formulation variables, such as the amount of polysorbate 80, glycerin, and carbomer copolymer as well as the area of oil-water interface were investigated. Polysorbate 80 was found to have the greatest influence on the drug distribution. It enhanced both the rate and extent of the drug distribution from oil to aqueous phase. Glycerin was found to slightly reduce the rate and extent of drug distribution of cyclosporine into the aqueous phase, probably by suppressing the solubilization capability of the micelles. Carbomer slowed down the diffusion of drug into the oil phase and shifted the equilibrium drug distribution towards the aqueous phase. Furthermore, increase in the interfacial area significantly increased the rate of drug diffusion across the oil-aqueous interface but had negligible effect on the extent of drug distribution. It is noteworthy that the experimental setup utilized a planar interface rather than an interface with curvature, which may have slightly underestimated the influence of globule size on equilibrium drug distribution. The findings of this study give insight into the drug distribution and diffusion in complex ophthalmic emulsions and assist with formulation design as well as development of in vitro methods to support BE assessment of ophthalmic emulsions.
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10.
Lipid Nanoparticles and Active Natural Compounds: A Perfect Combination for Pharmaceutical Applications.
Puglia, C, Pignatello, R, Fuochi, V, Furneri, PM, Lauro, MR, Santonocito, D, Cortesi, R, Esposito, E
Current medicinal chemistry. 2019;(24):4681-4696
Abstract
Phytochemicals represent an important class of bioactive compounds characterized by significant health benefits. Notwithstanding these important features, their potential therapeutic properties suffer from poor water solubility and membrane permeability limiting their approach to nutraceutical and pharmaceutical applications. Lipid nanoparticles are well known carrier systems endowed with high biodegradation and an extraordinary biocompatible chemical nature, successfully used as platform for advanced delivery of many active compounds, including the oral, topical and systemic routes. This article is aimed at reviewing the last ten years of studies about the application of lipid nanoparticles in active natural compounds reporting examples and advantages of these colloidal carrier systems.