Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of ...neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.
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Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin ...has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions.
To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential ...component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin–drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.
Polysaccharides (PSs) have been extensively studied in healthcare applications; here, we focus our attention on their use as components of nanomaterials in the management of cancer and inflammatory ...pathologies. Key advantages of PSs are easy availability, general biodegradability and biocompatibility, low or negligible toxicity, often a low immunogenicity and finally an ease of chemical modification. Here, we pay particular attention to the large family of amphiphilic PS derivatives (AMPDs); they are synthesized by modifying hydrophilic PSs with a variety of hydrophobic groups, which allow the constructs to self-assemble into various nanostructures in aqueous solution. This review focuses on AMPD-based self-assembled nanoparticles, from the chemical synthesis of AMPDs, through nanoparticle preparative strategies, to the most recent applications in cancer and inflammation management, including therapeutics, imaging and theranostics. We also offer an overview, which we feel lacks in the current literature, of the relation between the nature of the hydrophilic PSs and that of the hydrophobic components, of linkers, targeting groups and cross-linkers, and of the actual properties and in vivo fate of AMPD-based nanoparticles. Finally, we believe that this comprehensive insight into the possible effects of AMPDs’ structural components on the performance of nanosystems, can provide criteria for a rational and molecular level-based design of AMPDs.
Molecular design of AMPDs in view of their structural composition (i~v) and the applications of AMPD-based self-assembled NPs in cancer and inflammatory management Display omitted
Lyotropic liquid crystal systems, such as reversed bicontinuous cubic and hexagonal mesophases, are attracting more and more attention because of their unique microstructures and physicochemical ...properties. Various bioactive molecules such as chemical drugs, peptides and proteins can be solubilized in either aqueous or oil phase and be protected from hydrolysis or oxidation. Furthermore, several studies have demonstrated sustained release of bioactive molecules from reversed cubic and hexagonal mesophases. This article gives an overview of recent advances and current status of reversed cubic and hexagonal mesophases, especially with respect to their preparation methods and applications in the field of drug delivery. In addition, potential problems and possible future research directions are highlighted.
Curcumin-loaded PLGA-PEG-PLGA micelles significantly increased the distribution of curcumin in lung and brain and reduced uptake by liver and spleen.
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► Micelles were firstly prepared ...with this triblock copolymers using solvent-dialysis method and successfully encapsulated hydrophobic CUR. ► The pharmacokinetic parameters of CUR micelles were improved compared to the CUR solution, respectively. ► The biodistribution study in mice showed that the PLGA-PEG-PLGA micelle formulation decreased drug uptake by the liver and spleen, and increased the distribution of drug in lung and brain.
The aim of this study was to assess the potential of new copolymeric micelles to modify the pharmacokenetics and tissue distribution of Curcumin (CUR), a hydrophobic drug. In the present study, a poly (
d,
l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(
d,
l-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was synthesized and characterized by
1H NMR, gel permeation chromatography and FTIR analysis. The CUR-loaded PLGA-PEG-PLGA micelles were prepared by dialysis method and the physicochemical parameters of the micelles such as zeta potential, size distribution and drug encapsulation were characterized. The pharmacokinetics and biodistribution of CUR-loaded micelles in vivo were evaluated. The results showed that the zeta potential of CUR-loaded micelles was about −0.71
mV and the average size was 26.29
nm. CUR was encapsulated into PLGA-PEG-PLGA micelles with loading capacity of 6.4
±
0.02% and entrapment efficiency of 70
±
0.34%. The plasma AUC
(0–
∞
),
t
1/2α,
t
1/2β and MRT of CUR micelles were increased by 1.31, 2.48, 4.54 and 2.67 fold compared to the CUR solution, respectively. The biodistribution study in mice showed that the micelles decreased drug uptake by liver and spleen and enhanced drug distribution in lung and brain. These results suggested that PLGA-PEG-PLGA micelles would be a potential carrier for CUR.
•Novel chondroitin sulfate-based nanoparticles (PTX/CQE NPs) were initially prepared.•PTX/CQE NPs could exert enhanced chemo-photodynamic therapy in vitro and in vivo.•PTX/CQE NPs exhibited in vivo ...MDR inhibition and anti-metastasis efficacy.
As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.
Graphene-based nanomaterials have drawn abundant interest in various fields such as biomedicine in recent years. Thanks to the ultra-high surface area of single-layered graphene, higher molecular ...loading is obtained. In addition, easy modifications were acquired because of its ample oxygen-content functional groups. Owing to its excellent physical- chemical properties, graphene-based nanomaterials have been widely explored as novel nanovectors for disease theranostics. In this article, we gave a comprehensive review of graphenebased nanomaterials, including introduction about different members of graphene family nanomaterials (GFNs), various modifications, toxicity and biomedical applications of graphene- based derivatives. More attentions were given to phototherapy in this paper. The mechanisms of photothermal and photodynamic therapy were also offered. Finally, the prospects and challenges of the graphene-based nanomaterials were discussed in this review.
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•Glycyrrhetinic acid decorated polymer (GA-CMCA) was used to deliver quercetin (QC).•QC-GA-CMCA had smaller size and narrower size distribution than unmodified ones.•GA modification ...on conjugates could alter the in vitro release pattern of QC.•QC-GA-CMCA showed enhanced cytotoxicity and cell apoptosis rate.•QC-GA-CMCA could prolong drug circulation time in rats.
Quercetin (QC), a type of plant-based chemical, has been reported to own anticancer activity in vivo. However, the poor water solubility limits its pharmaceutical application. In this study, two kinds of QC-loaded self-aggregates based on O-carboxymethyl chitosan-cholic acid conjugates (CMCA) were developed to improve the drug bioavailability in which glycyrrhetinic acid (GA) modification was utilized in the nanocarrier fabrication (QC-GA-CMCA) or not (QC-CMCA). These self-aggregates were prepared by a modified ultrasound-dialysis method and the role of GA modification on the evaluation of QC-loaded self-aggregates was investigated. Transmission Electron Microscopy (TEM) images revealed the formation of spherical particles of both self-aggregates. Dynamic Light Scattering (DLS) analysis and UV–VIS spectroscopy showed that the QC-GA-CMCA had smaller size, narrower size distribution, higher drug loading and entrapment efficiency than corresponding QC-CMCA aggregates. QC-GA-CMCA showed more obvious sensitivity to acidic pH condition based on the zeta potential measurements at various pHs, and fastest drug release was observed at pH 5.7 for QC-CMCA while at pH 6.5 for QC-GA-CMCA. In addition, QC-GA-CMCA demonstrated enhanced cell cytotoxicity and higher cell apoptosis rate in vitro, and also higher AUC value and a prolonged residence time of drug in vivo.
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Paclitaxel (PTX) belongs to a class of taxane anti-tumor drug used for the clinic treatment of breast cancer, ovarian cancer, non-small-cell lung cancer, and so on. PTX has poor water ...solubility and oral bioavailability. It is generally administered via intravenous (i.v.) infusion. Traditional PTX injectable preparations contain Cremophor-EL and ethanol to improve its solubility, which would result in adverse reactions like severe hypersensitivity, neutropenia, etc. Adverse reactions can be reduced only by complicated pretreatment with glucocorticoid and antihistamines drugs and followed by PTX slow infusion for three hours, which has brought significant inconvenience to the patients. Though, a new-generation PTX formulation, Abraxane, free of Cremophor-EL and ethanol, is still being administrated by frequent i.v. infusions and extremely expensive. Therefore, non-injection administration of PTX is urgently needed to avoid the side effects as well as reduce inconvenience to the patients. Recently, a variety of non-injection drug delivery systems (DDSs) of PTX have been developed. This review aims to discuss the progress of non-injectable administration systems of PTX, including oral administration systems, vaginal administration systems, implantable DDSs, transdermal DDSs and intranasal administration for the future study and clinical applications.
