Showing papers on "Drug carrier published in 2006"
TL;DR: This work has shown that addition of PEG and PEG-containing copolymers to the surface of nanoparticles results in an increase in the blood circulation half-life of the particles by several orders of magnitude, and creates a hydrophilic protective layer around the nanoparticles that is able to repel the absorption of opsonin proteins via steric repulsion forces.
3,185 citations
TL;DR: This review will discuss some recent trends in using micelles as pharmaceutical carriers, including lipid-core micells, which may become the imaging agents of choice in different imaging modalities.
Abstract: Micelles, self-assembling nanosized colloidal particles with a hydrophobic core and hydrophilic shell are currently successfully used as pharmaceutical carriers for water-insoluble drugs and demonstrate a series of attractive properties as drug carriers. Among the micelle-forming compounds, amphiphilic copolymers, i.e., polymers consisting of hydrophobic block and hydrophilic block, are gaining an increasing attention. Polymeric micelles possess high stability both in vitro and in vivo and good biocompatibility, and can solubilize a broad variety of poorly soluble pharmaceuticals many of these drug-loaded micelles are currently at different stages of preclinical and clinical trials. Among polymeric micelles, a special group is formed by lipid-core micelles, i.e., micelles formed by conjugates of soluble copolymers with lipids (such as polyethylene glycol-phosphatidyl ethanolamine conjugate, PEG-PE). Polymeric micelles, including lipid-core micelles, carrying various reporter (contrast) groups may become the imaging agents of choice in different imaging modalities. All these micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention (EPR) effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block-copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. This review will discuss some recent trends in using micelles as pharmaceutical carriers.
1,685 citations
TL;DR: In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and alpha(v)beta(3)-specific cytotoxic response of these multifunctional polymeric micelles.
Abstract: We describe the development of multifunctional polymeric micelles with cancer-targeting capability via αvβ3 integrins, controlled drug delivery, and efficient magnetic resonance imaging (MRI) contrast characteristics. Doxorubicin and a cluster of superparamagnetic iron oxide (SPIO) nanoparticles were loaded successfully inside the micelle core. The presence of cRGD on the micelle surface resulted in the cancer-targeted delivery to αvβ3-expressing tumor cells. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and αvβ3-specific cytotoxic response of these multifunctional polymeric micelles.
1,201 citations
1,068 citations
TL;DR: Polymeric micelles are nanotechnology-based carrier systems that might exert the activity of potent bioactive compounds in a site-directed manner, ensuring their effectiveness and safety in the clinical use.
973 citations
TL;DR: Increasing the molecular weight of dextran statistically significantly reduced its tumor vascular permeability and had the highest accumulation in solid tumors but were largely concentrated near the vascular surface.
Abstract: BACKGROUND Delivery of anticancer therapeutic agents to solid tumors is problematic. Macromolecular drug carriers are an attractive alternative drug delivery method because they appear to target tumors and have limited toxicity in normal tissues. We investigated how molecular weight influences the accumulation of a model macromolecular drug carrier, dextran covalently linked to a fluorophore, in tumors. METHODS We used dextrans with molecular weights from 3.3 kDa to 2 MDa. Vascular permeability, accumulation, and three-dimensional penetration of these dextrans were simultaneously measured in solid tumors via a dorsal skin fold window chamber, intravital laser-scanning confocal microscopy, and custom image analysis. RESULTS Increasing the molecular weight of dextran statistically significantly reduced its vascular permeability by approximately two orders of magnitude (i.e., from 154 x 10(-7) cm/s, 95% confidence interval [CI] = 134 to 174 x 10(-7) cm/s, for 3.3-kDa dextran to 1.7 x 10(-7) cm/s, 95% CI = 0.7 to 2.6 x 10(-7) cm/s for 2-MDa dextran; P < .001, two-sided Kruskal-Wallis test) but increased its plasma half-life, which provided ample time for extravasation (i.e., to enter tumor tissue from the vasculature). Tumor accumulation was maximal for dextrans with molecular weights between 40 and 70 kDa. Dextrans of 3.3 and 10 kDa penetrated deeply (greater than 35 microm) and homogeneously into tumor tissue from the vessel wall. After a 30-minute period, a high concentration was observed only approximately 15 microm from the vessel wall for 40- to 70-kDa dextrans and only 5 microm for 2-MDa dextrans. CONCLUSIONS Increasing the molecular weight of dextran statistically significantly reduced its tumor vascular permeability. Dextrans of 40 and 70 kDa had the highest accumulation in solid tumors but were largely concentrated near the vascular surface.
853 citations
TL;DR: It is demonstrated here the effective delivery of a dye payload into cells using 2-nm core gold nanoparticles, with release occurring via place exchange of glutathione onto the particle surface.
Abstract: We demonstrate here the effective delivery of a dye payload into cells using 2-nm core gold nanoparticles, with release occurring via place exchange of glutathione onto the particle surface. In vitro experiments demonstrate effective release of drug analogues upon addition of glutathione. Cell culture experiments show rapid uptake of nanoparticle and effective release of payload. The role of glutathione in the release process was demonstrated through improved payload release upon transient increase in glutathione levels achieved via introduction of glutathione ethyl ester into the cell.
781 citations
TL;DR: The performance of calcium phosphate cements as carriers of different types of drugs, such as antibiotics, analgesics, anticancer, anti-inflammatory, as well as growth factors is reviewed.
656 citations
TL;DR: Microemulsions were found as an effective vehicle of the solubilization of certain drugs and as protecting medium for the entrapped of drugs from degradation, hydrolysis, and oxidation.
628 citations
TL;DR: The remarkable antitumor activity of dendrimer–DOX results from the ability of the d endrimer to favorably modulate the pharmacokinetics of attached DOX.
Abstract: The antitumor effect of doxorubicin (DOX) conjugated to a biodegradable dendrimer was evaluated in mice bearing C-26 colon carcinomas. An asymmetric biodegradable polyester dendrimer containing 8–10 wt % DOX was prepared. The design of the dendrimer carrier optimized blood circulation time through size and molecular architecture, drug loading through multiple attachment sites, solubility through PEGylation, and drug release through the use of pH-sensitive hydrazone linkages. In culture, dendrimer–DOX was >10 times less toxic than free DOX toward C-26 colon carcinoma cells after exposure for 72 h. Upon i.v. administration to BALB/c mice with s.c. C-26 tumors, dendrimer–DOX was eliminated from the serum with a half-life of 16 ± 1 h, and its tumor uptake was ninefold higher than i.v. administered free DOX at 48 h. In efficacy studies performed with BALB/c mice bearing s.c. C-26 tumors, a single i.v. injection of dendrimer–DOX at 20 mg/kg DOX equivalents 8 days after tumor implantation caused complete tumor regression and 100% survival of the mice over the 60-day experiment. No cures were achieved in tumor-implanted mice treated with free DOX at its maximum tolerated dose (6 mg/kg), drug-free dendrimer, or dendrimer–DOX in which the DOX was attached by means of a stable carbamate bond. The antitumor effect of dendrimer–DOX was similar to that of an equimolar dose of liposomal DOX (Doxil). The remarkable antitumor activity of dendrimer–DOX results from the ability of the dendrimer to favorably modulate the pharmacokinetics of attached DOX.
618 citations
TL;DR: The current synthetic advances in polymer-conjugation with different bioactive components of clinical importance are discussed and the strategies for reduction of steric hindrance and increase in reactivity of the polymers, drugs and bioactive agents are described.
TL;DR: This article aims to provide a comprehensive review of existing mathematical models and simulations of drug release from polymeric microspheres and of drug transport in adjacent tissues and to evaluate the application of existing models to nanoscale drug delivery systems specifically for hydrophobic and hydrophilic molecules.
TL;DR: An overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd–based contrast agents.
Abstract: In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed.
TL;DR: The polymersomes cause two-fold higher cell death in tumors than free drug and show quantitatively similar increases in maximum tolerated dose and drug accumulation within the tumors-suggesting promise for multi-drug delivery.
TL;DR: To develop targeted pharmaceutical carriers additionally capable of responding to certain local stimuli, such as decreased pH values in tumors or infarcts, targeted long-circulating PEGylated liposomes and PEG-phosphatidylethanolamine-based micelles have been prepared with several functions.
TL;DR: In this paper, a review of the physical properties of polymeric micelles is presented, including micellar association, morphology, size and stability, as well as their properties and characterization techniques.
Abstract: Polymeric micelles are nanoscopic core/shell structures formed by amphiphilic block copolymers. Both the inherent and modifiable properties of polymeric micelles make them particularly well suited for drug delivery purposes. An emphasis of this review has been placed on both the description and characterization techniques of the physical properties of polymeric micelles. Relevant properties discussed include micellar association, morphology, size and stability. These properties and characterization techniques are included to provide context for the known advantages and applications of polymeric micelles for drug delivery. The advantages and applications discussed include solubilization of poorly soluble molecules, sustained release and size advantages, and protection of encapsulated substances from degradation and metabolism. The three most widely studied block copolymer classes are characterized by their hydrophobic blocks, and are poly(propylene oxide), poly(L-amino acid)s and poly(ester)s. These three classes of block copolymers are reviewed with multiple examples of current research in which formulation techniques with polymeric micelles have been applied to some of the most challenging molecules in the pharmaceutical industry. The polymeric micelles used for drug delivery in these examples have shown the abilities to attenuate toxicities, enhance delivery to desired biological sites and improve the therapeutic efficacy of active pharmaceutical ingredients.
TL;DR: The results revealed that the encapsulation of verapamil in both calcium-alginate and calcium alginate-chitosan mixed beads exceeded 80% and the drug release mechanisms were either "anomalous transport" or "case-II transport".
TL;DR: A biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging and prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.
Abstract: We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.
TL;DR: Well-ordered mesoporous bioactive glasses with high specific surface area with high ability to induce hydroxyapatite (HAp) formation have been synthesized in aqueous solution by a two-step acid-catalyzed self-assembly process combined with hydrothermal treatment.
TL;DR: Two studies of light-responsive micellar aggregates of small-molecule surfactants suggest that any chromophores whose photoinduced structural rearrangements gives rise to a significant change in dipole moment could be used in designing light-dissociable BCP micelles based on the same principle.
Abstract: Micellar aggregates (core -shell micelles, vesicles, etc.) formed by amphiphilic block copolymers (BCPs) are being actively investigated as a nanocarrier system for controlled delivery of drugs and other biological substances. 1 Generally speaking, a good nanocarrier of drugs would be (1) stable during the circulation in the blood, allowing no release of encapsulated hydrophobic drugs, (2) able to accumulate specifically in the target site (e.g., tumors), and (3) once on target, able to release the carried drug quickly or in a controlled fashion. Each of these requirements has prompted a great deal of research efforts in the design, synthesis and exploitation of new BCPs. As far as the control of release is concerned, BCP micelles that can be disrupted by external stimuli, thus triggering the release of entrapped agents, are of particular interest. The stimuli studied so far not only include changes that BCP micelles in the body can experience, such as increase or decrease in pH, 2 in temperature 3 and exposure to oxidation reaction, 4 but also include sound 5 and light6-8 that can be applied from outside of the body for remote activation of the disruption of micelles. If the interaction of BCP micelles with light lead to their dissociation, photocontrolled release of encapsulated agents is possible. One obvious, and attractive, feature of stable, lightresponsive polymer micelles is that the release of the carried guest (not limited to drugs) could be started at required time (when light is applied) and at required location (where light exposure is directed to). This offers new perspectives in controlled release that would be difficult to realize using other stimuli. To obtain usable BCP-based nanocarriers for photocontrolled delivery applications, the development of effective designs of BCP structures and fundamental studies of their photoinduced dissociation and release processes are necessary. There are many studies of light-responsive micellar aggregates of small-molecule surfactants, 9-16 but very few reports on lightdissociable polymer micelles. 6-8 We first studied amphiphilic BCPs whose hydrophobic block is an azobenzene-containing side-chain liquid crystalline polymer (Azo-SCLCP). 6,7 We found that their core-shell micelles and vesicles in solution can be dissociated by UV light irradiation and re-formed upon visible light exposure, as a result of the reversible trans -ci photoisomerization of azobenzene side groups of the hydrophobic block. From a study of the mechanism of the reversible micellar dissociation, a general design principle for azobenzene-based light-dissociable BCP micelles has been suggested. 7 The azobenzene moiety should have a small (near zero) dipole moment in the trans form and a high dipole moment in the cis form (determined by the substituents on the azobenzene unit); when this is conjugated with a weakly hydrophilic block (determined by the chemical nature and the length of the block), the increase in polarity of the azobenzene polymer block under UV light (trans-cis isomerization taking place) can alter the hydrophilic/hydrophobic balance which results in dissociation of micelles, while the decrease in polarity upon visible light irradiation (reverse cis -trans isomerization occurring) shifts the hydrophilic/hydrophobic balance in the opposite direction which brings back the micelles. More importantly, these studies suggest that any chromophores whose photoinduced structural rearrangements gives rise to a significant change in dipole moment could be used in designing light-dissociable BCP micelles based on the same principle. If the photoinduced process is reversible, the micellar dissociation is reversible. More recently, we have demonstrated the efficiency of a different, and more general, strategy for designing BCPs whose micelles can undergo irreversible light-induced dissociation. 8
TL;DR: The purpose of this manuscript is to provide an update on the current status of polymeric micelles for each application and highlight important parameters that may lead to the development of successful polymeric mousellar systems for individual delivery requirements.
Abstract: Polymeric micelles have been the subject of many studies in the field of drug delivery for the past two decades. The interest has specifically been focused on the potential application of polymeric micelles in three major areas in drug delivery: drug solubilisation, controlled drug release and drug targeting. In this context, polymeric micelles consisting of poly(ethylene oxide)-b-poly(propylene oxide), poly(ethylene oxide)-b-poly(ester)s and poly(ethylene oxide)-b-poly(amino acid)s have shown a great promise and are in the front line of development for various applications. The purpose of this manuscript is to provide an update on the current status of polymeric micelles for each application and highlight important parameters that may lead to the development of successful polymeric micellar systems for individual delivery requirements.
TL;DR: It is shown that a strong magnetic field gradient at the tumour location accumulates the nanoparticles and electron microscope investigations show that the ferrofluids can be enriched in tumour tissue and tumour cells.
Abstract: Magnetic drug targeting employing nanoparticles as carriers is a promising cancer treatment avoiding side effects of conventional chemotherapy. We used iron oxide nanoparticles covered by starch derivatives with phosphate groups which bound mitoxantrone as chemotherapeutikum. In this letter we show that a strong magnetic field gradient at the tumour location accumulates the nanoparticles. Electron microscope investigations show that the ferrofluids can be enriched in tumour tissue and tumour cells.
TL;DR: The specific degradation profile and adjustable drug release behaviors by variation of fiber characteristics made the electrospun nonwoven mat a potential drug delivery system rather than polymer films and particles.
TL;DR: In this article, a semi-interpenetrating polymer network (IPN) microspheres of natural polymers, viz., gelatin and sodium carboxymethyl cellulose (NaCMC), were prepared by using glutaraldehyde (GA) as a crosslinker.
TL;DR: The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix and the bioadhesive property of the developed formulation was found to be significant (P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone.
TL;DR: The results support the concept of DEBs as an effective way to deliver drugs to tumor, and this new technology may prove to be a useful weapon against liver cancer.
Abstract: Background: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2).
Purpose: The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB.
Results: Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 μmol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially. Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal.
Conclusions: Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.
TL;DR: High initial microparticle porosities do not only lead to increased drug mobilities, but can also fundamentally alter the underlying mass transport mechanisms.
TL;DR: The results showed that besides their solubilizing effects, polymeric micelles could be useful as novel drug carriers for hydrophobic drugs.
TL;DR: It was found that even W/O microemulsions, which are expected to break upon dilution in the digestive tract, increase the permeability and bioavailability of drugs.
TL;DR: In this study it has been proved that using SLN as a drug carrier for oral administration of cyclosporine A a low variation in bioavailability of the drug and simultaneously avoiding the plasma peak typical of the first Sandimmun formulation can be achieved.