- Chitosan Glutamate-Coated Niosomes: A Proposal for Nose-to-Brain Delivery. [Journal Article]
- PPharmaceutics 2018 Mar 22; 10(2)
- The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal de...
The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration.
- Understanding the co-loading and releasing of doxorubicin and paclitaxel using chitosan functionalized single-walled carbon nanotubes by molecular dynamics simulations. [Journal Article]
- PCPhys Chem Chem Phys 2018 Mar 22
- Two widely used anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), possess distinct physical properties and chemotherapy specificity. In order to investigate their interaction mechanism with s...
Two widely used anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), possess distinct physical properties and chemotherapy specificity. In order to investigate their interaction mechanism with single-walled carbon nanotubes (SWCNTs), co-loading and releasing from the SWCNTs, all-atom molecular dynamics (MD) simulations were firstly carried out for different SWCNT systems, followed by binding free energy calculation with MM-PBSA. The results indicate that the co-loading of DOX and PTX onto the pristine SWCNT is exothermic and spontaneous. The DOX molecules predominantly interact with the SWCNT via π-π stacking through the conjugated aromatic rings, while the separated aromatic rings of PTX also primarily interact with the SWCNT through π-π stacking yet supplemented by an X-π (X = C-H, N-H and C[double bond, length as m-dash]O) interaction. Moreover, the strongest binding of DOX and PTX with the pristine SWCNT shows similar strength (ΔG: -32.0 vs. -33.8 kcal mol-1). For the chitosan functionalized SWCNT (f-SWCNT), the DOX and PTX molecules still prefer binding to the sidewall of the CNT rather than binding with the polymer, and the non-covalent functionalization of the SWCNT with chitosan decreases the binding of DOX and PTX with the sidewall of the f-SWCNT as compared with the DOX/PTX-SWCNT system (ΔG: -24.0 and -21.9 kcal mol-1). The protonation of chitosan and drug molecules further weakens the interaction between DOX/PTX and the f-SWCNT, and shows a consequent displacement of the drug molecules, triggering the release of the drugs. The variation of binding strength of the three systems (DOX/PTX-SWCNT, DOX/PTX-f-SWCNT, and DOXH+/PTXH+-f-SWCNT) was also discussed in terms of the histogram or frequency of the distance from the drugs to the SWCNT. In addition, the encapsulation of two DOX molecules by the f-SWCNT is considerably stronger than the binding of the other six drug molecules to the sidewall, indicating that the encapsulation of anticancer drugs may also play a very important role and should be considered in the drug delivery.
- Nanoparticle wrapping at small non-spherical vesicles: curvatures at play. [Journal Article]
- NNanoscale 2018 Mar 22
- Nanoparticles in biological systems encounter lipid-bilayer membranes as barriers. They interact with plasma membranes, membranous organelles, such as the endoplasmic reticulum and the Golgi apparatu...
Nanoparticles in biological systems encounter lipid-bilayer membranes as barriers. They interact with plasma membranes, membranous organelles, such as the endoplasmic reticulum and the Golgi apparatus, the nucleus, and intracellular and extracellular vesicles, such as autophagosomes, lysosomes, and exosomes. Extracellular vesicles have recently attracted particular attention, as they are involved in the transmission of biological signals and as regulators for biological processes. For example, exosomes, small vesicles containing proteins, mRNA, and miRNA, that are released by cells into the extracellular environment, have been suggested to participate in tumor metastasis. Furthermore, vesicles can be applied as targeted-drug-delivery systems. We systematically characterize wrapping of spherical nanoparticles that enter and exit vesicles, depending on particle size, vesicle size, vesicle reduced volume, and membrane spontaneous curvature. We predict the complex wrapping behavior, in particular for large particle-to-vesicle size ratios, where the shape changes of the free membrane contribute significantly to the deformation energy and where nanoparticle wrapping transitions and vesicle shape transitions are coupled. Partial-wrapped membrane-bound particles impose boundary conditions on the membrane that stabilise oblates and stomatocytes for particle entry, and prolates and stomatocytes for particle exit. Our results suggest that nanoparticles may stimulate autophagocytic engulfment, which would facilitate transport of the nanoparticles into lysosomes and would lead to subsequent degradation of nanoparticle-attached proteins.
- Self-nanoemulsifying drug-delivery systems improve oral absorption and antischistosomal activity of epiisopiloturine. [Journal Article]
- NNanomedicine (Lond) 2018 Mar 22
- CONCLUSIONS: Taken together, these results indicate that SNEDDS-EPI is efficient in reducing worm burden in comparison to treatment with the free version of EPI.
- RGD Peptide Based Non-viral Gene Delivery Vectors Targeting Integrin αvβ3for Cancer Therapy. [Journal Article]
- JDJ Drug Target 2018 Mar 22; :1-31
- Integrin αvβ3is restrictedly expressed on angiogenic blood vessels and tumor cells. It plays a key role in angiogenesis for tumor growth and metastasis. RGD peptide can specifically recognize the int...
Integrin αvβ3is restrictedly expressed on angiogenic blood vessels and tumor cells. It plays a key role in angiogenesis for tumor growth and metastasis. RGD peptide can specifically recognize the integrin αvβ3, which serve as targeted molecular for anti-angiogenesis strategies. Therefore, targeted delivery of therapeutics by RGD peptide based non-viral vectors to tumor vasculature and tumor cells is recognized as a promising approach for treating cancer. In this review, we illustrate the interaction between RGD peptide and integrin αvβ3from different perspectives. Meanwhile, four types of RGD peptide based non-viral gene delivery vectors for cancer therapy, including RGD based cationic polymers, lipids, peptides and hybrid systems, are summarized. The aim is to particularly highlight the enhanced therapeutic effects and specific targeting ability exhibited by these vectors for cancer gene therapy both in vitro and in vivo.
- Bio-inspired drug delivery systems: an emerging platform for targeted cancer therapy. [Review]
- BSBiomater Sci 2018 Mar 22
- The quest for an ideal cancer treatment has led to the exploration of a variety of platforms to facilitate highly desirable and efficient drug delivery. As most anticancer drugs possess therapeutic p...
The quest for an ideal cancer treatment has led to the exploration of a variety of platforms to facilitate highly desirable and efficient drug delivery. As most anticancer drugs possess therapeutic potency to destroy tumor cells, there is a need to steer the compounds to their required sites using site-specific drug delivery vehicles. This has inspired the investigation of various natural particulates and biomaterials for the purpose. Bio-inspired platforms that directly mimic natural components in the body have demonstrated their ability to serve as one of the most versatile and innovative drug delivery systems in cancer therapy and diagnosis. The primary advantage of this innovation lies in the fundamental changes in systemic biodistribution that non-native drug delivery does not possess. This review will try to provide a comprehensive understanding and a succinct evaluation of various intelligent bio-inspired delivery platforms, which have become prominent in recent studies. Recent innovative examples and their advantages and limitations as well as future clinical potential will also be thoroughly discussed.
- Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers. [Review]
- IJInt J Nanomedicine 2018; 13:1425-1442
- Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tum...
Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.
- Heart tissue repair and cardioprotection using drug delivery systems. [Review]
- MMaturitas 2018; 110:1-9
- The capacity of the heart to heal after a myocardial infarction is not enough to restore normal cardiac function. Fortunately, delivery of therapeutics such as stem cells, growth factors, exosomes an...
The capacity of the heart to heal after a myocardial infarction is not enough to restore normal cardiac function. Fortunately, delivery of therapeutics such as stem cells, growth factors, exosomes and small interfering ribonucleic acid (siRNA), among other bioactive molecules, has been shown to enhance heart repair and improve cardiac function. Furthermore, new delivery systems for these therapeutic agents have enhanced their regenerative and cardioprotective potential. In particular, nano- and microparticles (NPs and MPs) are promising. These systems may be administered directly in the infarcted myocardium or reach the heart after intravenous injection due to the enhanced permeability and retention effect or active targeting. Thus, NPs and MPs have made it possible to administer a wide range of potential drugs, including therapeutic molecules and/or stem cells, and evidence in favor of their use has been reported in several preclinical studies. Here, we review the studies done over the last 5 years using NPs and MPs loaded with therapeutics for repairing cardiac tissue after a myocardial infarction, and discuss some of the advances, challenges and future prospects in this field. In addition, we address the application of NPs and MPs for cardioprotective purposes.
- Towards the Identification of an In Vitro Tool for Assessing the Biological Behavior of Aerosol Supplied Nanomaterials. [Journal Article]
- IJInt J Environ Res Public Health 2018 Mar 21; 15(4)
- Nanoparticles (NP)-based inhalation systems for drug delivery can be administered in liquid form, by nebulization or using pressurized metered dose inhalers, and in solid form by means of dry powder ...
Nanoparticles (NP)-based inhalation systems for drug delivery can be administered in liquid form, by nebulization or using pressurized metered dose inhalers, and in solid form by means of dry powder inhalers. However, NP delivery to the lungs has many challenges including the formulation instability due to particle-particle interactions and subsequent aggregation, causing poor deposition in the small distal airways and subsequent alveolar macrophages activity, which could lead to inflammation. This work aims at providing an in vitro experimental design for investigating the correlation between the physico-chemical properties of NP, and their biological behavior, when they are used as NP-based inhalation treatments, comparing two different exposure systems. By means of an aerosol drug delivery nebulizer, human lung cells cultured at air-liquid interface (ALI) were exposed to two titanium dioxide NP (NM-100 and NM-101), obtained from the JRC repository. In parallel, ALI cultures were exposed to NP suspension by direct inoculation, i.e., by adding the NP suspensions on the apical side of the cell cultures with a pipette. The formulation stability of NP, measured as hydrodynamic size distributions, the cell viability, cell monolayer integrity, cell morphology and pro-inflammatory cytokines secretion were investigated. Our results demonstrated that the formulation stability of NM-100 and NM-101 was strongly dependent on the aggregation phenomena that occur in the conditions adopted for the biological experiments. Interestingly, comparable biological data between the two exposure methods used were observed, suggesting that the conventional exposure coupled to ALI culturing conditions offers a relevant in vitro tool for assessing the correlation between the physico-chemical properties of NP and their biological behavior, when NP are used as drug delivery systems.
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- The theranostic efficiency of tumor-specific, pH-responsive, peptide-modified, liposome-containing paclitaxel and superparamagnetic iron oxide nanoparticles. [Journal Article]
- IJInt J Nanomedicine 2018; 13:1495-1504
- CONCLUSIONS: Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI.