Showing papers on "Drug carrier published in 2014"
TL;DR: Recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases are highlighted.
Abstract: The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases.
1,186 citations
TL;DR: This review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field.
837 citations
TL;DR: It is demonstrated that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region and exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein.
Abstract: Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hun...
504 citations
TL;DR: This paper reviews the most significant advancements in protein nanoparticle technology and their use in drug delivery arena, and examines the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation.
Abstract: Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.
474 citations
TL;DR: The present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.
Abstract: Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.
471 citations
TL;DR: An original and simple thermal substitution method is reported to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees.
Abstract: Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.
364 citations
TL;DR: The dopamine polymerization method is a simple and versatile surface modification method, applicable to a variety of NP drug carriers irrespective of their chemical reactivity and the types of ligands.
Abstract: The surface of a polymeric nanoparticle (NP) is often functionalized with cell-interactive ligands and/or additional polymeric layers to control NP interaction with cells and proteins. However, such modification is not always straightforward when the surface is not chemically reactive. For this reason, most NP functionalization processes employ reactive linkers or coupling agents or involve prefunctionalization of the polymer, which are complicated and inefficient. Moreover, prefunctionalized polymers can lose the ability to encapsulate and retain a drug if the added ligands change the chemical properties of the polymer. To overcome this challenge, we use dopamine polymerization as a way of functionalizing NP surfaces. This method includes brief incubation of the preformed NPs in a weak alkaline solution of dopamine, followed by secondary incubation with desired ligands. Using this method, we have functionalized poly(lactic-co-glycolic acid) (PLGA) NPs with three representative surface modifiers: a small ...
353 citations
TL;DR: By applying beneficial features of EVs to liposomes and vice versa, improved drug carriers can be developed which will advance the field of nanomedicines and ultimately improve patient outcomes.
349 citations
TL;DR: Surface modification of SPIONs can open up the possibility of drug delivery to intracellular organelles, drug delivery across the blood–brain barrier, modifying metabolic diseases and a variety of other multimodal and/or theranostic applications.
Abstract: Introduction: Bearing in mind that many promising drug candidates have the problem of reaching their target site, the concept of advanced drug delivery can play a significant complementary role in shaping modern medicine. Among other nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential in nanomedicine. The intrinsic properties of SPIONs, such as inherent magnetism, broad safety margin and the availability of methods for fabrication and surface engineering, pave the way for diverse biomedical applications. SPIONs can achieve the highest drug targeting efficiency among carriers, since an external magnetic field locally applied to the target organ enhances the accumulation of magnetic nanoparticles in the drug site of action. Moreover, theranostic multifunctional SPIONs make simultaneous delivery and imaging possible. In spite of these favorable qualities, there are some toxicological concerns, such as oxidative stress, unpredictable cellular responses and i...
349 citations
TL;DR: It is hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels, and demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides.
Abstract: Biological systems are exquisitely sensitive to the location and timing of physiologic cues and drugs. This spatiotemporal sensitivity presents opportunities for developing new therapeutic approaches. Polymer-based delivery systems are used extensively for attaining localized, sustained release of bioactive molecules. However, these devices typically are designed to achieve a constant rate of release. We hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels. We demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides. Parallel in vitro studies demonstrated that the concept of applying temporally short, high-dose “bursts” of drug exposure could be applied to enhance the toxicity of mitoxantrone toward breast cancer cells. We thus used the hydrogel system in vivo to treat xenograft tumors with mitoxantrone, and found that daily ultrasound-stimulated drug release substantially reduced tumor growth compared with sustained drug release alone. This approach of digital drug release likely will be applicable to a broad variety of polymers and bioactive molecules, and is a potentially useful tool for studying how the timing of factor delivery controls cell fate in vivo.
347 citations
TL;DR: The mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, are described and how those interactions can promote drug release and tissue uptake are described.
TL;DR: This work reports the synthesis of polymer nanoparticles (NPs) that carry precise molar ratios of doxorubicin, camptothecin, and cisplatin that provide the first example of orthogonally triggered release of three drugs from single NPs.
Abstract: The synthesis of polymer therapeutics capable of controlled loading and synchronized release of multiple therapeutic agents remains a formidable challenge in drug delivery and synthetic polymer chemistry. Herein, we report the synthesis of polymer nanoparticles (NPs) that carry precise molar ratios of doxorubicin, camptothecin, and cisplatin. To our knowledge, this work provides the first example of orthogonally triggered release of three drugs from single NPs. The highly convergent synthetic approach opens the door to new NP-based combination therapies for cancer.
TL;DR: Different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are discussed, along with their characterization.
Abstract: Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.
TL;DR: It is shown that sequential self-assembly of the EGCG derivative with anticancer proteins forms stable micellar nanocomplexes (MNCs), which have greater anticancer effects in vitro and in vivo than the free protein.
Abstract: A green tea-based drug carrier offers a delivery system where both the drug and carrier possess therapeutic effects.
TL;DR: There is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.
Abstract: Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.
TL;DR: The current review article is focused on the engineering of the core of polymeric micelles for maximum therapeutic effect and for enhanced drug encapsulation capacity and getting useful insights into the controlled release mechanism.
Abstract: Though much progress has been made in drug delivery systems, the design of a suitable carrier for the delivery of hydrophobic drugs is still a major challenge for researchers. The use of micellar solutions of low molecular weight surfactants has been one of the popular methods for the solubilization of hydrophobic drugs; however, such surfactants suffer from high critical micelle concentration and concomitant low stabilities. In contrast to surfactants of low molecular masses, polymeric micelles are associated with general advantages like higher stability, tailorability, greater cargo capacity, non-toxicity and controlled drug release. Therefore, the current review article is focused on the engineering of the core of polymeric micelles for maximum therapeutic effect. For enhanced drug encapsulation capacity and getting useful insights into the controlled release mechanism we have reviewed the effects of temperature and pH on responsive polymeric micelles. The article also presents important research outcomes about mixed polymeric micelles as better drug carriers in comparison to single polymeric micelles.
TL;DR: The curcumin encapsulated in casein nanoparticles showed significantly improved anti-proliferation activity against human colorectal and pancreatic cancer cells and is promising to utilize lipophilic compounds in food or pharmaceutical industries.
Abstract: The poor water solubility and bioactivity of lipophilic phytochemicals can be potentially improved by delivery systems. In this study, a low-cost, low-energy, and organic solvent-free encapsulation technology was studied by utilizing the pH-dependent solubility properties of curcumin and self-assembly properties of sodium caseinate (NaCas). Curcumin was deprotonated and dissolved, while NaCas was dissociated at pH 12 and 21 °C for 30 min. The subsequent neutralization enabled the encapsulation of curcumin in self-assembled casein nanoparticles. The degradation of curcumin under encapsulation conditions was negligible based on visible light and nuclear magnetic resonance spectroscopy. The dissociation of NaCas at pH 12 and reassociation after neutralization were confirmed using dynamic light scattering and analytical ultracentrifugation. The curcumin encapsulated in casein nanoparticles showed significantly improved anti-proliferation activity against human colorectal and pancreatic cancer cells. The studied encapsulation method is promising to utilize lipophilic compounds in food or pharmaceutical industries.
TL;DR: Liposomes doped with porphyrin–phospholipid that are permeabilized directly by near-infrared light are described and spatial and temporal control of release of entrapped fluorophores following intratumoral injection are demonstrated.
Abstract: The delivery of therapeutic compounds to target tissues is a central challenge in treating disease. Externally controlled drug release systems hold potential to selectively enhance localized delivery. Here we describe liposomes doped with porphyrin–phospholipid that are permeabilized directly by near-infrared light. Molecular dynamics simulations identified a novel light-absorbing monomer esterified from clinically approved components predicted and experimentally demonstrated to give rise to a more stable porphyrin bilayer. Light-induced membrane permeabilization is enabled with liposomal inclusion of 10 molar % porphyrin– phospholipid and occurs in the absence of bulk or nanoscale heating. Liposomes reseal following laser exposure and permeability is modulated by varying porphyrin–phospholipid doping, irradiation intensity or irradiation duration. Porphyrin–phospholipid liposomes demonstrate spatial control of release of entrapped gentamicin and temporal control of release of entrapped fluorophores following intratumoral injection. Following systemic administration, laser irradiation enhances deposition of actively loaded doxorubicin in mouse xenografts, enabling an effective single-treatment antitumour therapy.
TL;DR: Phenomena relevant to drug delivery, such as non-spherical oscillations, shear stress, microstreaming, and jetting will be reviewed from both a theoretical and experimental perspective.
TL;DR: A pH-responsive charge-reversal polyelectrolyte and integrin αⅤβ3 mono-antibody functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and controlled release of DOX into cancer cells, likely to be an available candidate for targeted drug delivery in tumor therapy.
TL;DR: G gelatin modifications for immune system evasion, drug stabilization, and targeted delivery, as well as gelatin composite systems based on ceramics, naturally-occurring polymers, and synthetic polymers are discussed.
TL;DR: The importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations, and emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity.
Abstract: Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10–100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.
TL;DR: This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems as well as natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles.
Abstract: Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids.
Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.
TL;DR: Aldoxorubicin, a prodrug of doxorubricin, which binds covalently to the cysteine-34 position of circulating albumin, is in advanced clinical trials with a registration phase 3 trial for soft tissue sarcoma initiated in Q1 2014 as discussed by the authors.
TL;DR: The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles.
TL;DR: Zr-based MOF nanoparticles were applied as efficient carriers for alendronate delivery, and an unprecedented drug loading capacity was achieved thanks to the inherent drug anchorages of Zr-O clusters therein.
TL;DR: It is shown how GCMC simulation is able to predict the macroscopic performance of new porous MOFs in drug delivery applications, providing useful molecular-level insights and giving thermodynamic and structural details of the process.
Abstract: A series of bio-compatible metal–organic frameworks (MOFs) have been studied as potential carriers for drug delivery applications. Grand canonical Monte Carlo (GCMC) simulations were performed to study the adsorption of the model drug ibuprofen. Simulations were first validated with available experimental data for ibuprofen adsorption and release in MIL-53, MIL-100 and MIL-101. In the second stage, the study was extended to three additional MOFs with interesting properties in terms of bio-compatibility and porosity: CDMOF-1, based on edible precursors; MOF-74 containing a highly biocompatible metal (Mg); and BioMOF-100, a mesoporous MOF with extremely high pore volume. By comparing with experimental data, we show how GCMC simulation is able to predict the macroscopic performance of new porous MOFs in drug delivery applications, providing useful molecular-level insights and giving thermodynamic and structural details of the process. Adsorption isotherms, snapshots, energy of adsorption and radial distribution functions were used to analyse the drug delivery process.
TL;DR: This study establishes NCPs as a promising drug delivery platform for cancer therapy by using them as nanotherapeutics with enhanced antitumor activities and reports the self-assembly of zinc bisphosphonate N CPs that carry 48±3 wt% cisplatin prodrug and 45±5 wt%.
Abstract: Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes and shapes, high drug loadings, ease of surface modification and intrinsic biodegradability. Here we report the self-assembly of zinc bisphosphonate NCPs that carry 48 ± 3 wt% cisplatin prodrug and 45 ± 5 wt% oxaliplatin prodrug. In vivo pharmacokinetic studies in mice show minimal uptake of pegylated NCPs by the mononuclear phagocyte system and excellent blood circulation half-lives of 16.4 ± 2.9 and 12.0 ± 3.9 h for the NCPs carrying cisplatin and oxaliplatin, respectively. In all tumour xenograft models evaluated, including CT26 colon cancer, H460 lung cancer and AsPC-1 pancreatic cancer, pegylated NCPs show superior potency and efficacy compared with free drugs. As the first example of using NCPs as nanotherapeutics with enhanced antitumour activities, this study establishes NCPs as a promising drug delivery platform for cancer therapy.
TL;DR: The synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells and folate receptor-mediated cellular binding/uptake was demonstrated.
TL;DR: Solution pH, crosslinker concentration and monomer to SA weight ratio of the hydrogels were found to have a strong effect on adsorption and in vitro release profile of the drug from the gel matrix.