Showing papers on "Drug carrier published in 2015"

Mesoporous Silica Nanoparticles in Target Drug Delivery System: A Review

Abstract: Due to lack of specification and solubility of drug molecules, patients have to take high doses of the drug to achieve the desired therapeutic effects for the treatment of diseases. To solve these problems, there are various drug carriers present in the pharmaceuticals, which can used to deliver therapeutic agents to the target site in the body. Mesoporous silica materials become known as a promising candidate that can overcome above problems and produce effects in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles (MSNs) are widely used as a delivery reagent because silica possesses favorable chemical properties, thermal stability, and biocompatibility. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release of the target site. The properties of mesoporous, including pore size, high drug loading, and porosity as well as the surface properties, can be altered depending on additives used to prepare MSNs. Active surface enables functionalization to changed surface properties and link therapeutic molecules. They are used as widely in the field of diagnosis, target drug delivery, bio-sensing, cellular uptake, etc., in the bio-medical field. This review aims to present the state of knowledge of silica containing mesoporous nanoparticles and specific application in various biomedical fields.

The importance of nanoparticle shape in cancer drug delivery

Abstract: Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and ...

Transformable liquid-metal nanomedicine

Abstract: To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery.

Abstract: Yulin Li,*,†,‡ Dina Maciel,† Joaõ Rodrigues,*,† Xiangyang Shi,*,†,§ and Helena Tomaś*,† †CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada 9000-390, Funchal, Portugal ‡The State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People’s Republic of China College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China

Polymer-Grafted Mesoporous Silica Nanoparticles as Ultrasound-Responsive Drug Carriers

Abstract: A new ultrasound-responsive system based on mesoporous silica nanoparticles was developed for biomedical applications, grafting a copolymer on their surface that acts as gatekeeper of the pores. The nanoparticles can be loaded with a cargo at low temperature (4 °C), taking advantage of the open conformation that the polymer presents under these conditions. Then, at 37 °C the copolymer collapses closing the pore entrances and allowing the nanoparticles to carry the drugs at physiological temperature without premature release, which is of great importance when dealing with cytotoxic drugs in cancer treatments. Upon ultrasound irradiation, the sensitive polymer changes its hydrophobicity and, therefore, its conformation toward coil-like opening the gates and releasing the cargo. These hybrid nanoparticles have been shown to be noncytotoxic and can be internalized into LNCaP cells retaining their ultrasound-responsive capability in the cytoplasm of the cells. Moreover, doxorubicin-loaded hybrid MSNs were incubated with LNCaP cells to show their capacity to induce cell death only when the nanoparticles had been exposed to ultrasound. This work demonstrates that our hybrid-MSNs can be triggered by remote stimuli, which is of capital importance for future applications in drug delivery and cancer therapy.

Use of a Lipid-Coated Mesoporous Silica Nanoparticle Platform for Synergistic Gemcitabine and Paclitaxel Delivery to Human Pancreatic Cancer in Mice

Abstract: Recently, a commercial albumin-bound paclitaxel (PTX) nanocarrier (Abraxane) was approved as the first new drug for pancreatic ductal adenocarcinoma in almost a decade. PTX improves the pharmaceutical efficacy of the first-line pancreatic cancer drug, gemcitabine (GEM), through suppression of the tumor stroma and inhibiting the expression of the GEM-inactivating enzyme, cytidine deaminase (CDA). We asked, therefore, whether it was possible to develop a mesoporous silica nanoparticle (MSNP) carrier for pancreatic cancer to co-deliver a synergistic GEM/PTX combination. High drug loading was achieved by a custom-designed coated lipid film technique to encapsulate a calculated dose of GEM (40 wt %) by using a supported lipid bilayer (LB). The uniform coating of the 65 nm nanoparticles by a lipid membrane allowed incorporation of a sublethal amount of hydrophobic PTX, which could be co-delivered with GEM in pancreatic cells and tumors. We demonstrate that ratiometric PTX incorporation and delivery by our LB-MS...

Sequential Drug Release and Enhanced Photothermal and Photoacoustic Effect of Hybrid Reduced Graphene Oxide-Loaded Ultrasmall Gold Nanorod Vesicles for Cancer Therapy.

Abstract: We report a hybrid reduced graphene oxide (rGO)-loaded ultrasmall plasmonic gold nanorod vesicle (rGO-AuNRVe) (∼65 nm in size) with remarkably amplified photoacoustic (PA) performance and photothermal effects. The hybrid vesicle also exhibits a high loading capacity of doxorubicin (DOX), as both the cavity of the vesicle and the large surface area of the encapsulated rGO can be used for loading DOX, making it an excellent drug carrier. The loaded DOX is released sequentially: near-infrared photothermal heating induces DOX release from the vesicular cavity, and an intracellular acidic environment induces DOX release from the rGO surface. Positron emission tomography imaging showed high passive U87MG tumor accumulation of 64Cu-labeled rGO-AuNRVes (∼9.7% ID/g at 24 h postinjection) and strong PA signal in the tumor region. Single intravenous injection of rGO-AuNRVe-DOX followed by low-power-density 808 nm laser irradiation (0.25 W/cm2) revealed effective inhibition of tumor growth due to the combination of c...

Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance

Abstract: Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.

Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges

Abstract: Various drug delivery approaches can be used to maximize therapeutic efficacy and minimize side effects, by impacting absorption, distribution, metabolism, and elimination (ADME) of a drug compound. For those drugs with poor water solubility or low permeability, techniques such as amorphous solid dispersion, liposomes, and complexations have been used to improve their oral bioavailability. Modified release (MR) formulations have been widely used to improve patient compliance, as well as to reduce side effects, especially for those drugs with short half-lives or narrow therapeutic windows. More than ten drugs using sterile long-acting release (LAR) formulations with clear clinical benefit have been successfully marketed. Furthermore, drug delivery systems have been used in delaying drug clearance processes. Additionally, modifying the in vivo drug distribution using targeted delivery systems has significantly improved oncology treatments. All the drug delivery approaches have their advantages and limitations. For both brand and generic drugs, the achievement of consistent quality and therapeutic performance using drug delivery systems can also pose serious challenges in developing a drug for the market, which requires close collaboration among industry, academia, and regulatory agencies. With the advent of personalized medicines, there will be great opportunities and challenges in utilizing drug delivery systems to provide better products and services for patients.

Margination of micro- and nano-particles in blood flow and its effect on drug delivery.

Abstract: Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their margination properties (migration toward walls) in the microvasculature. To investigate margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.

pH-activated nanoparticles for controlled topical delivery of farnesol to disrupt oral biofilm virulence.

Abstract: Development of effective therapies to control oral biofilms is challenging, as topically introduced agents must avoid rapid clearance from biofilm–tooth interfaces while targeting biofilm microenvironments. Additionally, exopolysaccharides-matrix and acidification of biofilm microenvironments are associated with cariogenic (caries-producing) biofilm virulence. Thus, nanoparticle carriers capable of binding to hydroxyapatite (HA), saliva-coated HA (sHA), and exopolysaccharides with enhanced drug release at acidic pH were developed. Nanoparticles are formed from diblock copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA), butyl methacrylate (BMA), and 2-propylacrylic acid (PAA) (p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA)) that self-assemble into ∼21 nm cationic nanoparticles. Nanoparticles exhibit outstanding adsorption affinities (∼244 L-mmol–1) to negatively charged HA, sHA, and exopolysaccharide-coated sHA due to strong electrostatic interactions via multivalent tertiary amines of p(DMAEMA). Owi...

pH-Responsive Capsules Engineered from Metal-Phenolic Networks for Anticancer Drug Delivery.

Abstract: A new class of pH-responsive capsules based on metal-phenolic networks (MPNs) for anticancer drug loading, delivery and release is reported. The fabrication of drug-loaded MPN capsules, which is based on the formation of coordination complexes between natural polyphenols and metal ions over a drug-coated template, represents a rapid strategy to engineer robust and versatile drug delivery carriers.

Calcium carbonate nanoparticles as cancer drug delivery system

Abstract: Introduction: Calcium carbonate (CaCO3) has broad biomedical utilizations owing to its availability, low cost, safety, biocompatibility, pH-sensitivity and slow biodegradability. Recently, there has been widespread interest in their application as drug delivery systems for different groups of drugs. Among them, CaCO3 nanoparticles have exhibited promising potential as drug carriers targeting cancer tissues and cells. The pH-dependent properties, alongside the potential to be functionalized with targeting agents give them the unique property that can be used in targeted delivery systems for anticancer drugs. Also, due to the slow degradation of CaCO3 matrices, these nanoparticles can be used as sustained release systems to retain drugs in cancer tissues for longer times after administration.Areas covered: Development of drug delivery carriers using CaCO3 nanoparticles has been reviewed. The current state of CaCO3 nanoparticles as cancer drug delivery systems with focus on their special properties like pH-s...

Polyethylenimine-grafted cellulose nanofibril aerogels as versatile vehicles for drug delivery.

Abstract: Aerogels from polyethylenimine-grafted cellulose nanofibrils (CNFs-PEI) were developed for the first time as a novel drug delivery system. The morphology and structure of the CNFs before and after chemical modification were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Water-soluble sodium salicylate (NaSA) was used as a model drug for the investigation of drug loading and release performance. The CNFs-PEI aerogels exhibited a high drug loading capability (287.39 mg/g), and the drug adsorption process could be well described by Langmuir isotherm and pseudo-second-order kinetics models. Drug release experiments demonstrated a sustained and controlled release behavior of the aerogels highly dependent on pH and temperature. This process followed quite well the pseudo-second-order release kinetics. Owing to the unique pH- and temperature-responsiveness together with their excellent biodegradability and biocompatibility, the CNFs-PEI aerogels were very promising as a new generation of controlled drug delivery carriers, offering simple and safe alternatives to the conventional systems from synthetic polymers.

Ceramic Nanoparticles: Fabrication Methods and Applications in Drug Delivery.

Abstract: Ceramic nanoparticles are primarily made up of oxides, carbides, phosphates and carbonates of metals and metalloids such as calcium, titanium, silicon, etc. They have a wide range of applications due to a number of favourable properties, such as high heat resistance and chemical inertness. Out of all the areas of ceramic nanoparticles applications, biomedical field is the most explored one. In the biomedical field, ceramic nanoparticles are considered to be excellent carriers for drugs, genes, proteins, imaging agents etc. To be able to act as a good and successful drug delivery agent, various characteristics of nanoparticles need to be controlled, such as size range, surface properties, porosity, surface area to volume ratio, etc. In achieving these properties on the favourable side, the method of preparation and a good control over process variables play a key role. Choosing a suitable method to prepare nanoparticles, along with loading of significant amount of drug(s) leads to development of effective drug delivery systems which are being explored to a great extent. Ceramic nanoparticles have been successfully used as drug delivery systems against a number of diseases, such as bacterial infections, glaucoma, etc., and most widely, against cancer. This review gives a detailed account of commonly used methods for synthesising nanoparticles of various ceramic materials, along with an overview of their recent research status in the field of drug delivery.

Applications of Magnetic Nanoparticles in Targeted Drug Delivery System.

Abstract: Magnetic nanoparticles (MNPs) are a special kind of nanomaterials and widely used in biomedical technology applications. Currently they are popularly customized for disease detection and treatment, particularly as drug carriers in drug targeted delivery systems, as a therapeutic in hyperthermia (treating tumors with heat), and as contrast agents in magnetic resonance imaging (MRI). Due to their biocompatibility and superparamagnetic properties, MNPs as next generation drug carriers have great attraction. Although the potential benefits of MNPs are considerable, any potential toxicity associated with these MNPs should be identified distinctly. The drug loading capability and the biomedical properties of MNPs generated by different surface coatings are the most sensitive parameters in toxicity. A lot of organic and inorganic materials are utilized as coating materials for surface functionalization and reducing toxicity of MNPs. pH or temperature sensitivity materials are widely used to manage drug loading and targeted release. In addition, MNPs can be controlled and directed to the desired pathological region by using external magnetic files (EMF). The realization of targeted drug delivery has decreased the dosage and improved the efficiency of drugs, which results in reduced side effects to normal tissues. This review discussed the possible organ toxicities of MNPs and their current advances as a drug delivery vehicle.

Biocompatible PEG‐Chitosan@Carbon Dots Hybrid Nanogels for Two‐Photon Fluorescence Imaging, Near‐Infrared Light/pH Dual‐Responsive Drug Carrier, and Synergistic Therapy

Abstract: Stimuli-responsive nanogels have gained signifi cant progress because of their great potential for applications in intelligent drug delivery and other biomedical fi elds. [ 1–4 ] Recently, much attention has been focused on the integration of stimuli-responsive polymer nanogels with inorganic nanoparticles (NPs) to combine the biosensing or bioimaging ability with the controlled drug delivery function. [ 5–10 ] A key attribute of such responsive hybrid nanogels as drug delivery systems is their ability to regulate the drug release under specifi c environments or stimuli, which can signifi cantly improve the therapeutic effi cacy at pathological sites but reduce the systemic side effects. [ 11 ] Both endogenous and exogenous activations can be used to regulate the drug release from their carriers. [ 12–14 ] The endogenous activation can be realized by the variation of specifi c physiochemical characteristics of the pathological microenvironment. [ 15–17 ] For example, many pathological processes in tumor tissue and intracellular endosome/lysosome decrease the local pH by 1–2.5 pH units or increase the local temperature by 1–5 °C in comparison with that of blood and normal tissues. [ 18–20 ] On the other hand, the exogenous activation that can remotely control the drug release at a desired site and time is considered crucial to boost the drug effi cacy in cancer treatment while minimizing side effects. [ 21–26 ] Among all external stimuli including light and magnetic fi eld, near-infrared (NIR) light is the most favored for controlling the drug release due to its simple operation, low energy absorption, maximum penetration, and minimum side effects for human tissue and organs. [ 27,28 ] So far, nanostructured gold (Au) has been commonly integrated into the stimuli-responsive polymer nanogels to realize simultaneous NIR light-triggered drug release and cell imaging. [ 29–34 ] However, several disadvantages are associated with the noble metal NPs for their use in biomedical areas, including the Biocompatible PEG-Chitosan@Carbon Dots Hybrid Nanogels for Two-Photon Fluorescence Imaging, Near-Infrared Light/pH Dual-Responsive Drug Carrier, and Synergistic Therapy

Microfluidics for Advanced Drug Delivery Systems

Abstract: Considerable efforts have been devoted towards developing effective drug delivery methods. Microfluidic systems, with their capability for precise handling and transport of small liquid quantities, have emerged as a promising platform for designing advanced drug delivery systems. Thus, microfluidic systems have been increasingly used for fabrication of drug carriers or direct drug delivery to a targeted tissue. In this review, the recent advances in these areas are critically reviewed and the shortcomings and opportunities are discussed. In addition, we highlight the efforts towards developing smart drug delivery platforms with integrated sensing and drug delivery components.

Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Π–Π Stacking Stabilized Polymeric Micelles

Abstract: Treatment of cancer patients with taxane-based chemotherapeutics, such as paclitaxel (PTX), is complicated by their narrow therapeutic index. Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of PTX, as they can be tailored to encapsulate large amounts of hydrophobic drugs and achiv prolonged circulation kinetics. As a result, PTX deposition in tumors is increased, while drug exposure to healthy tissues is reduced. However, many PTX-loaded micelle formulations suffer from low stability and fast drug release in the circulation, limiting their suitability for systemic drug targeting. To overcome these limitations, we have developed PTX-loaded micelles which are stable without chemical cross-linking and covalent drug attachment. These micelles are characterized by excellent loading capacity and strong drug retention, attributed to π–π stacking interaction between PTX and the aromatic groups of the polymer chains in the micellar core. The micelles are based on methoxy poly(ethylene gl...