Showing papers on "Drug carrier published in 2019"

Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.

Abstract: Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

Exosomes from M1-Polarized Macrophages Enhance Paclitaxel Antitumor Activity by Activating Macrophages-Mediated Inflammation

Abstract: Objective: Exosomes (Exos) are membrane-encased vesicles derived by nearly all cell types for intercellular communication and regulation. They also received attention for their use as natural therapeutic platforms and drug delivery system. Classically activated M1 macrophages suppress tumor growth by releasing pro-inflammatory factors. This study investigated the suitability of M1-exosomes (M1-Exos) as drug carrier and their effect on the NF-κB signal pathway and further detected whether macrophages repolarization can potentiate the antitumor activities of chemotherapeutics. Methods: M1-Exos were isolated from M1-macrophages by ultracentrifugation and characterized by transmission electron, nanoparticle tracking analysis, dynamic light scattering and western blot. Then M1-Exos were used as Paclitaxel (PTX) carriers to prepare a nano-formulation (PTX- M1-Exos). A relatively simple slight sonication method was used to prepare the drug delivery system (PTX-M1-Exos). The cytotoxicity of PTX-M1-Exos on cancer cells was detected by MTT and flow cytometry in vitro. 4T1 tumor bearing mice were used to perform the therapeutic effect of PTX-M1-Exos in vivo. Results: The expression of caspase-3 in breast cancer cells was increased when co-incubated with macrophages in the presence of M1-Exos in vitro. The production of pro-inflammatory cytokines was increased after exposure of macrophages in M1-Exos. M1-Exos provided a pro-inflammatory environment which enhanced the anti-tumor activity via caspase-3 mediated pathway. The treatment of M1-Exos to the tumor bearing mice exhibit anti-tumor effects in vivo. Meanwhile, the treatment of PTX-M1-Exos demonstrated higher anti-tumor effects than the M1-Exos or PTX group. Conclusion: The results in our study indicate that the M1-Exos act as the carrier to deliver PTX into the tumor tissues, and also enhance the anti-tumor effects of chemotherapeutics in tumor bearing mice.

Corona Composition Can Affect the Mechanisms Cells Use to Internalize Nanoparticles.

Abstract: Nanosized objects, such as nanoparticles and other drug carriers used in nanomedicine, once in contact with biological environments are modified by adsorption of biomolecules on their surface. The ...

Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

Abstract: The versatile electrospinning technique is recognized as an efficient strategy to deliver active pharmaceutical ingredients and has gained tremendous progress in drug delivery, tissue engineering, cancer therapy, and disease diagnosis. Numerous drug delivery systems fabricated through electrospinning regarding the carrier compositions, drug incorporation techniques, release kinetics, and the subsequent therapeutic efficacy are presented herein. Targeting for distinct applications, the composition of drug carriers vary from natural/synthetic polymers/blends, inorganic materials, and even hybrids. Various drug incorporation approaches through electrospinning are thoroughly discussed with respect to the principles, benefits, and limitations. To meet the various requirements in actual sophisticated in vivo environments and to overcome the limitations of a single carrier system, feasible combinations of multiple drug-inclusion processes via electrospinning could be employed to achieve programmed, multi-staged, or stimuli-triggered release of multiple drugs. The therapeutic efficacy of the designed electrospun drug-eluting systems is further verified in multiple biomedical applications and is comprehensively overviewed, demonstrating promising potential to address a variety of clinical challenges.

Framework nucleic acids as programmable carrier for transdermal drug delivery.

Abstract: DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. However, rapid serum disintegration leads to low bioavailability at targeted sites following systemic administration, hindering their biomedical applications. Here we demonstrate transdermal delivery of framework nucleic acids (FNAs) through topical applications. By designing FNAs with distinct shapes and sizes, we interrogate their penetration on mice and human skin explant. Skin histology reveals size-dependent penetration, with FNAs ≤75 nm effectively reaching dermis layer. 17 nm-tetrahedral FNAs show greatest penetration to 350 µm from skin periphery. Importantly, structural integrity is maintained during the skin penetration. Employing a mouse melanoma model, topical application of doxorubicin-loaded FNAs accommodates ≥2-fold improvement in drug accumulation and tumor inhibition relative to topically-applied free doxorubicin, or doxorubicin loaded in liposomes and polymeric nanoparticles. Programmable penetration with minimal systemic biodistribution underlines FNA potential as localized transdermal drug delivery carriers. DNA nanostructures hold great promise for drug delivery, but systemic administration is problematic. Here, the authors demonstrate that framework nucleic acids (FNAs) improve drug accumulation in tumours in topical application and that penetration depth is controllable through adjusting FNA size.

Overcoming the Reticuloendothelial System Barrier to Drug Delivery with a “Don’t-Eat-Us” Strategy

Abstract: Overcoming the reticuloendothelial system (RES) has long been a vital challenge to nanoparticles as drug carriers. Modification of nanoparticles with polyethylene glycol helps them avoid clearance by macrophages but also suppresses their internalization by target cells. To overcome this paradox, we developed an RES-specific blocking system utilizing a "don't-eat-us" strategy. First, a CD47-derived, enzyme-resistant peptide ligand was designed and placed on liposomes (d-self-peptide-labeled liposome, DSL). After mainline administration, DSL was quickly adsorbed onto hepatic phagocyte membranes (including those of Kupffer cells and liver sinusoidal endothelial cells), forming a long-lasting mask that enclosed the cell membranes and thus reducing interactions between phagocytes and subsequently injected nanoparticles. Compared with blank conventional liposomes (CL), DSL blocked the RES at a much lower dose, and the effect was sustained for a much longer time, highly prolonging the elimination half-life of the subsequently injected nanoparticles. This "don't-eat-us" strategy by DSL was further verified on the brain-targeted delivery against a cryptococcal meningitis model, providing dramatically enhanced brain accumulation of the targeted delivery system and superior therapeutic outcome of model drug Amphotericin B compared with CL. Our study demonstrates a strategy that blocks the RES by masking phagocyte surfaces to prolong nanoparticle circulation time without excess modification and illustrates its utility in enhancing nanoparticle delivery.

Exosomes as Drug Carriers for Cancer Therapy

Abstract: Exosomes, biological extracellular vesicles, have recently begun to find use in targeted drug delivery in solid tumor research. Ranging from 30-120 nm in size, exosomes are secreted from cells and isolated from bodily fluids. Exosomes provide a unique material platform due to their characteristics, including physical properties such as stability, biocompatibility, permeability, low toxicity, and low immunogenicity-all critical to the success of any nanoparticle drug delivery system. In addition to traditional chemotherapeutics, natural products and RNA have been encapsulated for the treatment of breast, pancreatic, lung, prostate cancers, and glioblastoma. This review discusses current research on exosomes for drug delivery to solid tumors.

Cocktail Strategy Based on Spatio-Temporally Controlled Nano Device Improves Therapy of Breast Cancer.

Abstract: Metastatic breast cancer may be resistant to chemo-immunotherapy due to the existence of cancer stem cells (CSC). Also, the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing the therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti-CSC agent thioridazine (THZ), and the PD-1/PD-L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure. The particle size shrinks when the nanoparticle transfers from circulation to tumor tissues, favoring both pharmacokinetics and cellular uptake, meanwhile achieving sequential drug release where needed. This nano device, named PM@THL, increases the intratumoral drug concentrations in mice and exhibits significant anticancer efficacy, with tumor inhibiting rate of 93.45% and lung metastasis suppression rate of 97.64%. It also reduces the proportion of CSC and enhances the T cells infiltration in tumor tissues, and thus prolongs the survival of mice. The cocktail therapy based on the spatio-temporally controlled nano device will be a promising strategy for treating breast cancer.

A polydopamine-based platform for anti-cancer drug delivery

Abstract: Cancer is the second leading cause of death in the world with around 9.6 million deaths in 2018, approximately 70% of which occurred in the middle- and low-income countries; moreover, the economic impact of cancer is significant and escalating day by day. The total annual economic cost of cancer treatment in 2010 was estimated at approximately US$ 1.16 trillion. Researchers have explored cancer mitigation therapies such as chemo-thermal therapy, chemo-photothermal therapy and photodynamic–photothermal therapy. These combinational therapies facilitate better control on the tunability of the carrier for effectively diminishing cancer cells than individual therapies such as chemotherapy, photothermal therapy and targeted therapy. All these therapies come under novel drug delivery systems in which anti-cancer drugs attack the cancerous cells due to various stimuli (e.g. pH, thermal, UV, IR, acoustic and magnetic)-responsive properties of the anti-cancer drug carriers. Compared to conventional drug delivery systems, the novel drug delivery systems have several advantages such as targeted drug release, sustained and consistent blood levels within the therapeutic window, and decreased dosing frequency. Among the numerous polymeric carriers developed for drug delivery, polydopamine has been found to be more suitable as a carrier for these drug delivery functions due to its easy and cost-effective fabrication, excellent biocompatibility, multi-drug carrier capacity and stimuli sensitivity. Therefore, in this review, we have explored polydopamine-based carriers for anti-cancer drug delivery systems to mitigate cancer and simultaneously discussed basic synthesis routes for polydopamine.

Ethylcellulose-A Pharmaceutical Excipient with Multidirectional Application in Drug Dosage Forms Development.

Abstract: Polymers constitute the most important group of excipients utilized in modern pharmaceutical technology, playing an essential role in the development of drug dosage forms. Synthetic, semisynthetic, and natural polymeric materials offer opportunities to overcome different formulative challenges and to design novel dosage forms for controlled release or for site-specific drug delivery. They are extensively used to design therapeutic systems, modify drug release, or mask unpleasant drug taste. Cellulose derivatives are characterized by different physicochemical properties, such as swellability, viscosity, biodegradability, pH dependency, or mucoadhesion, which determine their use in industry. One cellulose derivative with widespread application is ethylcellulose. Ethylcellulose is used in pharmaceutical technology as a coating agent, flavoring fixative, binder, filler, film-former, drug carrier, or stabilizer. The aim of this article is to provide a broad overview of ethylcellulose utilization for pharmaceutical purposes, with particular emphasis on its multidirectional role in the development of oral and topical drug dosage forms.

Application and design of esterase-responsive nanoparticles for cancer therapy

Abstract: Nanoparticles have been developed for tumor treatment due to the enhanced permeability and retention effects. However, lack of specific cancer cells selectivity results in low delivery efficiency and undesired side effects. In that case, the stimuli-responsive nanoparticles system designed for the specific structure and physicochemical properties of tumors have attracted more and more attention of researchers. Esterase-responsive nanoparticle system is widely used due to the overexpressed esterase in tumor cells. For a rational designed esterase-responsive nanoparticle, ester bonds and nanoparticle structures are the key characters. In this review, we overviewed the design of esterase-responsive nanoparticles, including ester bonds design and nano-structure design, and analyzed the fitness of each design for different application. In the end, the outlook of esterase-responsive nanoparticle is looking forward.

One-Pot Synthesis of DOX@Covalent Organic Framework with Enhanced Chemotherapeutic Efficacy

Abstract: Covalent organic frameworks (COFs) have attracted great attention across diverse research fields. However, only a few reports about the biomedical application of COFs are found in the literature. Attributed to the highly porous and tunable structure, as well as good thermal stability, COFs show great potential as drug carriers for chemotherapy. In this work, doxorubicin (DOX) was successfully in situ loaded into a COF by a one-pot method for the first time. The resultant DOX@COF platform exhibited high drug-loading capacity (32.1 wt %) and pH-responsive release property. In vitro and in vivo experiments demonstrated its good biocompatibility and enhanced antitumor efficacy.

Doxorubicin-loaded nanoscale metal-organic framework for tumor-targeting combined chemotherapy and chemodynamic therapy.

Abstract: Doxorubicin (DOX) as a traditional chemotherapy drug is restricted in clinical applications due to its poor therapeutic activity and severe side effects. Herein, we prepared a metal–organic framework (MOF) MIL-100 by a microwave-assisted synthesis and DOX was loaded in MIL-100 and then, hyaluronic acid (HA) was modified on the surface of MIL-100 to give DMH NPs. The DMH NPs possessed the following advantages: (1) MIL-100 could serve as a drug carrier with a high DOX loading efficiency; MIL-100 could also generate a hydroxyl radical (˙OH) in the presence of H2O2 for chemodynamic therapy (CDT) via a Fenton-like reaction. (2) To improve the dispersibility of MIL-100, HA was modified on the surface of MIL-100, which could endow MIL-100 with a targeting ability towards tumor tissues. (3) DMH NPs could enhance antitumor efficacy and reduce drug-related toxicity though the combination of chemotherapy and chemodynamic therapy. DMH NPs have enormous potential as a candidate for reducing the systemic toxicity and improving the treatment effect for breast cancer.

Polysaccharides in Ocular Drug Delivery

Abstract: Polysaccharides, such as cellulose, hyaluronic acid, alginic acid, and chitosan, as well as polysaccharide derivatives, have been successfully used to augment drug delivery in the treatment of ocular pathologies. The properties of polysaccharides can be extensively modified to optimize ocular drug formulations and to obtain biocompatible and biodegradable drugs with improved bioavailability and tailored pharmacological effects. This review discusses the available polysaccharide choices for overcoming the difficulties associated with ocular drug delivery, and it explores the reasons for the dependence between the physicochemical properties of polysaccharide-based drug carriers and their efficiency in different formulations and applications. Polysaccharides will continue to be of great interest to researchers endeavoring to develop ophthalmic drugs with improved effectiveness and safety.

Degradable Drug Carriers: Vanishing Mesoporous Silica Nanoparticles

Abstract: The versatile potential of mesoporous silica nanoparticles (MSNs) as drug delivery agents for cytotoxic or chemically sensitive (macro)molecules has been demonstrated in numerous in vitro and in vi...