Showing papers on "Drug carrier published in 2018"
TL;DR: This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications.
Abstract: Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.
1,891 citations
TL;DR: The latest works on various novel formulations loaded with various anti‐Alzheimer agents are discussed, which underlines the fact that majority of work related to the nose‐to‐brain delivery of anti‐AD drugs is limited only up to preclinical studies.
331 citations
TL;DR: This review describes the new trends in nanomaterials based drug delivery systems mainly using biopolymers such as proteins (silk fibroin, collagen, gelatin and albumin) and polysaccharides (chitosan, alginate, cellulose and starch).
303 citations
TL;DR: In vitro and in vivo studies demonstrate that PEG-CCM@APTES-COF-1 is a smart carrier for drug delivery with superior stability, intrinsic biodegradability, high DOX loading capacity, strong and stable fluorescence, prolonged circulation time and improved drug accumulation in tumors.
Abstract: Covalent organic frameworks (COFs) as drug-delivery carriers have been mostly evaluated in vitro due to the lack of COFs nanocarriers that are suitable for in vivo studies. Here we develop a series of water-dispersible polymer-COF nanocomposites through the assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and amine-functionalized COFs (APTES-COF-1) for in vitro and in vivo drug delivery. The real-time fluorescence response shows efficient tracking of the COF-based materials upon cellular uptake and anticancer drug (doxorubicin (DOX)) release. Notably, in vitro and in vivo studies demonstrate that PEG-CCM@APTES-COF-1 is a smart carrier for drug delivery with superior stability, intrinsic biodegradability, high DOX loading capacity, strong and stable fluorescence, prolonged circulation time and improved drug accumulation in tumors. More intriguingly, PEG350-CCM@APTES-COF-1 presents an effective targeting strategy for brain research. We envisage that PEG-CCM@APTES-COF-1 nanocomposites represent a great promise toward the development of a multifunctional platform for cancer-targeted in vivo drug delivery.
299 citations
TL;DR: A series of injectable conductive hydrogels based on chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD) with "smart" delivery vehicles with electro-responsiveness and pH-responsive properties for triggered and localized release of drugs are designed.
299 citations
TL;DR: This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS, presented here in terms of their specific functions.
Abstract: This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy.
265 citations
TL;DR: Different strategies including crosslinking and non-crosslinking approaches designed to stabilize micelles are reviewed and perspectives on future research directions are offered.
Abstract: Micelles have been studied as drug delivery carriers for decades. Their use can potentially result in high drug accumulation at the target site through the enhanced permeability and retention effect. Nevertheless, the lack of stability of micelles in the physiological environment limits their efficacy as a drug carrier. In particular, micelles tend to disassociate and prematurely release the encapsulated drugs, lowering delivery efficacy and creating toxicity concerns. Many efforts to enhance the stability of micelles have focused mainly on decreasing the critical micelle forming concentration and improving blood circulation. Herein, we review different strategies including crosslinking and non-crosslinking approaches designed to stabilize micelles and offer perspectives on future research directions.
263 citations
TL;DR: Serum albumin, a natural ligand carrier that is highly concentrated and long-circulating in the blood, has shown remarkable promise as a carrier for anti-cancer agents.
255 citations
TL;DR: It was showed that hyaluronic acid would have broad prospects for drug delivery and had good biocompatibility, biodegradability, and nonimmunogenicity.
Abstract: Hyaluronic acid has good biocompatibility, biodegradability, and nonimmunogenicity. In addition, it has the ability to recognize specific receptors that are overexpressed on the surface of tumor cells, and cancer drugs can be targeted to the tumor cells to better kill them. Therefore, hyaluronic acid has attracted much attention as drug delivery vehicle. Herein, the application of hyaluronic acid as carrier in drug delivery was analyzed and summarized in detail. It showed that hyaluronic acid would have broad prospects for drug delivery.
249 citations
TL;DR: The past and current techniques available for fabricating and remotely controlling drug delivery systems are reviewed and the application of new technologies (e.g. 3D printing) in this field are addressed.
202 citations
TL;DR: The utility of recent ligand‐directed liposome approaches, with a focus on dual‐ligand liposomes, for the treatment of solid tumors are discussed and the drawbacks limiting their progression to clinical adoption are examined.
TL;DR: In vivo anti-tumor experiments demonstrate the high tumor inhibition rate of photothermal-chemotherapy group with a significant synergistic effect, and the biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy.
TL;DR: This review will focus on the potential of pH-sensitive micells in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations.
TL;DR: In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs, and have a broad application prospect as a nasal drug delivery carrier.
Abstract: Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography-tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Conclusion Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier.
TL;DR: Polymer–lipid micelles with an ultralow undetectable critical micelle concentration make ultrastable drug carriers that significantly enhance therapeutic outcomes in a mouse model of melanoma.
Abstract: Conventional micellar carriers disassemble into free surfactants when diluted at concentrations below the critical micelle concentration (CMC). This limits the bioavailability in vivo of injected hydrophobic drugs encapsulated in micellar systems. Here, we show that a micelle comprising a superhydrophilic zwitterionic polymer domain and a superhydrophobic lipid domain has an undetectable CMC below 10−6 mM—a value that is orders of magnitude lower than the CMCs (>10−3 mM) of typical micellar systems. We also show that zwitterionic moieties or zwitterionic polymers added to a micelle solution stabilize the micelles at concentrations below their inherent CMC. In a mouse model of melanoma, ultralow-CMC micelles encapsulating docetaxel led to the complete eradication of tumours, whereas conventional docetaxel micellar formulations did not reverse tumour growth. Ultralow-CMC micelles might become next-generation carriers for drug delivery. Polymer–lipid micelles with an ultralow undetectable critical micelle concentration make ultrastable drug carriers that significantly enhance therapeutic outcomes in a mouse model of melanoma.
TL;DR: This review article highlights medically oriented micro-/nano-motors, in particular the ones created for targeted drug delivery, and discusses their current limitations and possibilities toward in vivo applications.
Abstract: Micro- and nano-motors are emerging as novel drug delivery platforms, offering advantages such as rapid drug transport, high tissue penetration and motion controllability. They can be propelled and/or guided by endogenous (i.e., chemotaxis) or exogenous stimuli (e.g., ultrasound, magnetic fields, light) toward the area of interest. Moreover, such stimuli can be used to trigger the release of a therapeutic payload when the motor reaches certain location in order to improve the drug targeting. In this review article, we highlight medically oriented micro-/nano-motors, in particular the ones created for targeted drug delivery, and discuss their current limitations and possibilities toward in vivo applications.
TL;DR: This review summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin.
Abstract: Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.
TL;DR: The most significant advantages of using dendrimers in nanomedicine are their high biocompatibility, good water solubility, and their entry through an endocytosis process.
Abstract: For the first time, an overview of dendrimers in combination with natural products and analogues as anti-cancer agents is presented. This reflects the development of drug delivery systems, such as dendrimers, to tackle cancers. The most significant advantages of using dendrimers in nanomedicine are their high biocompatibility, good water solubility, and their entry - with or without encapsulated, complexed or conjugated drugs - through an endocytosis process. This strategy has accelerated over the years in order to develop nanosystems as nanocarriers, to decrease the intrinsic toxicity of anti-cancer agents, to decrease the drug side effects, to increase the efficacy of the treatment, and consequently to improve patient compliance.
TL;DR: In vivo study showed that A33Ab-US-Exo/Dox had an excellent tumor targeting ability, and was able to inhibit tumor growth and prolong the survival of the mice with reduced cardiotoxicity.
TL;DR: Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell.
TL;DR: This review summarizes the use of physical (or supramolecular) gels derived from low molecular weight compounds for the encapsulation and controlled release of small therapeutic molecules.
Abstract: Pharmaceutical drugs with low water solubility have always received great attention within the scientific community. The reduced bioavailability and the need of frequent administrations have motivated the investigation of new drug delivery systems. Within this context, drug carriers that release their payload in a sustained way and hence reduce the administration rate are highly demanded. One interesting strategy to meet these requirements is the entrapment of the drugs into gels. So far, the most investigated materials for such drug-loaded gels are derived from polymers and based on covalent linkages. However, over the last decade the use of physical (or supramolecular) gels derived from low molecular weight compounds has experienced strong growth in this field, mainly due to important properties such as injectability, stimuli responsiveness and ease of synthesis. This review summarizes the use of supramolecular gels for the encapsulation and controlled release of small therapeutic molecules.
TL;DR: Gd3+‐doped monolayered‐double‐hydroxide nanosheets are prepared via a facile bottom‐up synthesis method, with a precisely controlled composition and uniform morphology, providing new perspectives in the design of multifunctional nanomedicine, which shows promising applications in controlled drug delivery and cancer theranostics.
Abstract: 2D nanomaterials have attracted considerable research interest in drug delivery systems, owing to their intriguing quantum size and surface effect. Herein, Gd3+ -doped monolayered-double-hydroxide (MLDH) nanosheets are prepared via a facile bottom-up synthesis method, with a precisely controlled composition and uniform morphology. MLDH nanosheets as drug carrier are demonstrated in coloading of doxorubicin and indocyanine green (DOX&ICG), with an ultrahigh drug loading content (LC) of 797.36% and an encapsulation efficiency (EE) of 99.67%. This is, as far as it is known, the highest LC level at nearly 100% of EE among previously reported 2D drug delivery systems so far. Interestingly, the as-prepared DOX&ICG/MLDH composite material shows both pH-controlled and near-infrared-irradiation-induced DOX release, which holds a promise in stimulated drug release. An in vivo dual-mode imaging, including near-infrared fluorescence and magnetic resonance imaging, enables a noninvasive visualization of distribution profiles at the tumor site. In addition, in vitro and in vivo therapeutic evaluations demonstrate an excellent trimode synergetic anticancer activity and superior biocompatibility of DOX&ICG/MLDH. Therefore, MLDH nanosheets provide new perspectives in the design of multifunctional nanomedicine, which shows promising applications in controlled drug delivery and cancer theranostics.
TL;DR: Cellular uptake results of DOX-GQDs-RGD conjugates indicate that not only DOX but also some GQDs penetrated into cell nuclei after 16 h of incubation, which suggests the possibility for G QDs serving as pH-sensitive drug carriers.
Abstract: A novel drug delivery system based on arginine-glycine-aspartic acid (RGD)-conjugated graphene quantum dots (GQDs) was synthesized and utilized to load the antitumor drug doxorubicin (DOX) for targeted cancer fluorescence imaging as well as tracking and monitoring drug delivery without the need for external dyes. The inherent stable fluorescence of GQDs enables real-time monitoring of the cellular uptake of the DOX-GQDs-RGD nano-assembly and the consequent release of DOX. The release of DOX demonstrated strong pH dependence and implies hydrogen-bonding interaction between GQDs and DOX, an observation that suggests the possibility for GQDs serving as pH-sensitive drug carriers. As a nanocarrier, GQDs unlinked with DOX were nontoxic to U251 human glioma cells. Compared to free DOX, DOX-GQDs-RGD conjugates demonstrated substantial cytotoxicity to U251 glioma cells within a broad range of DOX concentrations. After applying the GQDs as drug carriers, the drug efficacy of DOX improved without concomitant DOX dosage increases. Cellular uptake results of DOX-GQDs-RGD conjugates indicate that not only DOX but also some GQDs penetrated into cell nuclei after 16 h of incubation. This enhancement combined with efficient nuclear delivery improved the cytotoxicity of DOX dramatically. This type of drug delivery system based on GQDs may find widespread applications in biomedicine.
TL;DR: This work reviews the recent advances in design and synthesis of biodegradable dendrimers, as well as their applications in fabricating drug delivery systems, with the aim of providing researchers in the related fields a good understanding of biodesgradabledendrimer for drug delivery.
TL;DR: This review is to provide a comprehensive overview of the various applications of PDA in tumor targeted drug delivery systems and to gain insight into the release behavior of the drug-loaded PDA-based nanocarriers.
TL;DR: The in vivo anticancer experiments indicate that CCM@ MOF-Zr(DTBA) exhibits much higher antitumor efficacy than free CCM, and this strategy for constructing responsive MOFs-based nanocarriers might open new possibilities for the application of MOFs in drug delivery, molecular imaging, or theranostics.
Abstract: Metal–organic frameworks (MOFs), which are a unique class of hybrid porous materials built from metal ions and organic ligands, have attracted significant interest in recent years as a promising platform for controlled drug delivery. Current approaches for creating MOFs-based responsive drug carriers involve encapsulation of stimuli-responsive compositions into MOFs or postsynthetic surface modification with sensitive molecules. In this study, we developed a novel intrinsic redox-responsive MOFs carrier, MOF-M(DTBA) (M = Fe, Al or Zr) by using iron, aluminum, or zirconium as metal nodes and 4,4′-dithiobisbenzoic acid (4,4′-DTBA) as the organic ligand. The disulfide bond in 4,4′-DTBA is cleavable by glutathione (GSH), which is often overexpressed in tumor cells. It was found that MOF-Zr(DTBA) synthesized at 40 °C displayed the appropriate size and properties as a drug carrier. By incorporating curcumin (CCM) into MOF-Zr(DTBA), CCM@MOF-Zr(DTBA) nanoparticles were obtained that displayed a faster releasing b...
TL;DR: An overview of the techniques used to characterize drug and drug carrier diffusion is provided, and the advantages and disadvantages of the different models available are discussed to highlight the information they can afford.
TL;DR: A targeted drug delivery system that is accurately and quantitatively predicted to self-assemble into nanoparticles based on the molecular structures of precursor molecules, which are the drugs themselves.
Abstract: Development of targeted nanoparticle drug carriers often requires complex synthetic schemes involving both supramolecular self-assembly and chemical modification. These processes are generally difficult to predict, execute, and control. We describe herein a targeted drug delivery system that is accurately and quantitatively predicted to self-assemble into nanoparticles based on the molecular structures of precursor molecules, which are the drugs themselves. The drugs assemble with the aid of sulfated indocyanines into particles with ultrahigh drug loadings of up to 90%. We devised quantitative structure-nanoparticle assembly prediction (QSNAP) models to identify and validate electrotopological molecular descriptors as highly predictive indicators of nano-assembly and nanoparticle size. The resulting nanoparticles selectively targeted kinase inhibitors to caveolin-1-expressing human colon cancer and autochthonous liver cancer models to yield striking therapeutic effects while avoiding pERK inhibition in healthy skin. This finding enables the computational design of nanomedicines based on quantitative models for drug payload selection. Molecular simulations reveal the self-assembly of small molecules into nanoparticle drug carriers. Targeting of colon and liver cancer cells by the nanoparticles via kinase inhibitors is employed in anti-tumour therapy in vivo.
TL;DR: Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase are shown to have a significant impact on the size of PNPs, and it is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.
Abstract: Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. We systematically investigated the factors that could impact the size of PNPs fabricated by nano-precipitation. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase were shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, Dpw. It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.
TL;DR: An overview of chemical properties, mechanisms of CDs on drug solubilization, stabilization and permeation, along with their toxicological profiles relevant to nasal and ocular administration, are provided and discussed.
Abstract: Cyclodextrins (CDs) are recognized as promising pharmaceutical excipients due to their unique ability to form water-soluble inclusion complexes with various poorly soluble compounds. The numerous investigations on CDs and their use in nanomedicine have received considerable attention in the last three decades, leading to the rapid development of new CD-containing formulations that significantly facilitate targeted drug delivery and controlled drug release, with consequent improvements in drug bioavailability. This MiniReview highlights the efficacy and recent uses of CDs for non-invasive drug delivery. Using ophthalmic and nasal drug delivery as examples, an overview of chemical properties, mechanisms of CDs on drug solubilization, stabilization and permeation, along with their toxicological profiles relevant to nasal and ocular administration, are provided and discussed. The recent development and application of CD-based nanocarrier systems for targeted drug delivery are summarized.