Type Of Drug Carrier Research Articles

Research Progress on the Preparation of Inorganic/Natural Materials Composite Microspheres

Microspheres are a new type of drug carrier with great potential for development and application. Natural polymers have good biocompatibility, biodegradability, and are easily dispersed in living organisms, making them suitable for preparing microspheres. Inorganic materials (mainly inorganic minerals) have excellent mechanical properties and are inexpensive and easy to obtain. Through the coupling and hybridization of natural polymers and inorganic materials, they can complement each other's advantages and synergistically enhance efficiency, resulting in many excellent physical and chemical properties. Inorganic materials/natural polymer composite microspheres can be prepared by modifying natural polymers with inorganic materials through various methods such as emulsification crosslinking, solution mixing, in-situ synthesis, extrusion, etc. The application of inorganic materials/natural polymer composite microspheres in drug delivery systems has significant sustained-release effects, is safe and non-toxic, and the cost of carrier materials is relatively low, which has certain significance for the development of new drug carriers. This article reviews the recent research on the preparation, drug loading and release properties of inorganic material/natural polymer composite microspheres, analyzes the advantages and disadvantages of commonly used preparation methods, and looks forward to the development direction of composite microspheres.

Targeted drug delivery in pulmonary therapy based on adhesion and transmission of nanocarriers designed with a metal-organic framework.

With the recent increase in lung diseases, especially with the onset of the coronavirus pandemic, the design of a highly efficient and optimal targeted drug delivery system for the lungs is crucial in inhaler-based delivery systems. This study aimed to design a magnetic field-assisted targeted drug delivery system to the lungs using three types of metal-organic frameworks (MOFs) and nanoliposomes. The optimization of the system was based on three main parameters: the surface density of the nanocarriers' (NCs) adherence to each of the lung branches, the amount of drug transferred to each branch, and the toxicity based on the rate of nanocarrier delivery to the branches. The study investigated the effect of increasing the diameter of the drug carriers and the amount of drug loaded onto the NCs in improving drug delivery to targeted areas of the lung. Results showed that the presence of a magnetic field significantly increased the adhesion of NCs to the targeted branches. The application of a magnetic field and the type of drug carrier had a significant effect on drug delivery downstream of the lung and reduced drug toxicity. The study found that Fe3O4@UiO-66 (iron-oxide nanoparticle attached to the surface of UiO-66, a type of MOF) and Fe3O4@PAA/AuNCs/ZIF-8 carriers, (iron-oxide nanoparticle attached to a hybrid structure composed of three different materials: poly (acrylic acid) (PAA), gold nanoclusters (AuNCs), and zeolitic imidazolate framework-8 (ZIF-8)), had the greatest drug delivery rate in diameters above 200 nm and less than 200 nm, respectively.

Design and applications of liposome-in-gel as carriers for cancer therapy

Cancer has long been a hot research topic, and recent years have witnessed the incidence of cancer trending toward younger individuals with great socioeconomic burden. Even with surgery, therapeutic agents serve as the mainstay to combat cancer in the clinic. Intensive research on nanomaterials can overcome the shortcomings of conventional drug delivery approaches, such as the lack of selectivity for targeted regions, poor stability against degradation, and uncontrolled drug release behavior. Over the years, different types of drug carriers have been developed for cancer therapy. One of these is liposome-in-gel (LP–Gel), which has combined the merits of both liposomes and hydrogels, and has emerged as a versatile carrier for cancer therapy. LP–Gel hybrids have addressed the lack of stability of conventional liposomes against pH and ionic strength while displaying higher efficiency of delivery hydrophilic drugs as compared to conventional gels. They can be classified into three types according to their assembled structure, are characterized by their nontoxicity, biodegradability, and flexibility for clinical use, and can be mainly categorized based on their controlled release, transmucosal delivery, and transdermal delivery properties for anticancer therapy. This review covers the recent progress on the applications of LP–Gel hybrids for anticancer therapy.

Development and characterization of DEC-205 receptor targeted Potentilla anserina L polysaccharide PLGA nanoparticles as an antigen delivery system to enhance in vitro and in vivo immune responses in mice

Potentilla anserina L polysaccharide (PAP) is known to regulate immunity. Poly(lactic-co-glycolicacid) (PLGA) is a type of drug carrier with biocompatibility and biodegradable USFDA approved polymer, which possesses the advantages of high safety and good sustained-release effect. The DEC205 receptor, a type I membrane protein, is widely distributed on the surface of macrophages and dendritic cells (DCs) and plays a key role in antigen recognition and presentation. In this study, we prepared Potentilla anserina L polysaccharide PLGA nanoparticles targeting DEC205 receptor (DEC205-PAPP) and characterized the nanoparticles with regards to their effects on immune activation in vitro and in vivo. In vitro, DEC205-PAPP promoted the uptake activity of macrophages and increased the secretion of NO and cytokines (IFN-γ, IL-4, IL-6, and GM-CSF), up-regulated the expression of CD80+, CD86+. In vivo, DEC205-PAPP elevated the immune organ index, induced DC maturation, promoted T lymphocyte proliferation and differentiation, and increased the levels of antigen-specific IgG antibody and cytokines (IFN-γ, IL-4), which prolonged the residence time of the OVA antigen in the immune organs and the lymph nodes. In conclusion, DEC205-PAPP had a slow-release effect, induced humoral and cellular immune responses, and could potentially be used as an effective antigen-targeted delivery system.

Control of drug release from cotton fabric by nanofibrous mat

A drug delivery system (DDSs) was developed in the present study based on textile substrates as drug carriers and electrospun nanofibers as a controller of release rate. Three types of drugs consisting of ciprofloxacin (CIP), clotrimazole (CLO), and benzalkonium chloride (BEN) were loaded into the cover glass (CG) and cotton fabrics (CF1 and CF2) separately. Then, the drug-loaded substrates were coated with polycaprolactone (PCL) and polycaprolactone/gelatin (PCL/Gel) nanofibers with various thicknesses. The morphology and hydrophilicity of the electrospun nanofibers and the release profile of drug-loaded samples were investigated. FTIR, XRD, and in vitro biodegradability analysis were analyzed to characterize the drug delivery system. A morphological study of electrospun fibers showed the mean diameter of the PCL and PCL/Gel nanofibers 127 ± 25 and 178 ± 38 nm, respectively. The drug delivery assay revealed that various factors affect the rate of drug releases, such as the type of drug, the type of drug carrier, and the thickness of the covered nanofibers. The study highlights the ability of drugs to load substrates with coated nanofibers as controlled drug delivery systems. In conclusion, it is shown that the obtained samples are excellent candidates for future wound dressing applications.

Solubilization and changes of physicochemical properties of baicalin by nano sponge, and toxicity of zebrafish liver

As a new type of drug carrier, nano-sponge (NS) can remarkably improve the solubility of poorly soluble drug components, significantly increase the efficacy of drugs and their bioavailability. Baicalin (BA) has many biological activities, such as anti-inflammatory, bacteriostatic and etc. But due to its poor solubility, BA cannot play a role in the clinic. Therefore, it is urgent to find a suitable solubilization technology to improve the solubility of BA. In this paper, we optimized the preparation process of NS based on β-cyclodextrin (β-CD), and then prepared the baicalin nano-sponges (BA-NS). The successful preparation of BA-NS was verified by modern analysis methods. BA loading capacity and efficiency (BLC and BLE), solubilizing effect, in vitro release rate and liver toxicity were investigated. The results showed that the BLC and BLE were 18.02 ± 0.36% and 86.64 ± 0.86%, solubility in water was 31 times than that of pure BA, and release rate in different media could reach 80%. Zebrafish liver toxicity test showed no obvious toxicity. The above results showed that NS had a significant solubilizing effect on BA and was safe and non-toxic, and proved that NS maybe have broad prospects in the research of poorly soluble drugs.

Freeze-drying of liposomal nanohybrid cerasomes with cryoprotectants: In vitro and in vivo evaluation

ABSTRACTLiposomal nanohybrid cerasomes as a new type of drug carrier has been widely applied in the controlled release of drugs. However, such vesicles containing polysiloxane networks on the surface were liable to aggregate during the process of freeze-drying for routine storage. To solve this problem, several previously reported cryoprotectants including sucrose, mannitol, sodium alginate, and glucose were chosen for protecting the 10-hydroxycamptothecin-loaded liposomal nanohybrid cerasomes (The drug encapsulation efficiency was of 67.31 ± 7.42% and the drug loading content was of 6.73 ± 0.74%.) in freeze-drying process. It was found that liposomal nanohybrid cerasomes treated with mannitol can be well dispersed, and the results of particle size and zeta potential showed that the drug-loaded vesicles were well protected with mannitol. In vitro drug release and in vivo pharmacokinetic study showed that the optimal addition amount of mannitol was twice the mass of the drug-loaded vesicles, whereby the cumulative release profile and the pharmacokinetic parameters were similar in the freeze-dried and fresh vesicles.

Liposome-Coated Iron Fumarate Metal-Organic Framework Nanoparticles for Combination Therapy.

One of the main problems for effective treatment of cancer is resistances, which often require combination therapy—for effective treatment. While there are already some potential drug carriers—e.g., liposomes, available for treatment—the effective loading and retention of the desired drug ratio can be challenging. To address this challenge, we propose a new type of drug carrier: liposome-coated metal-organic framework (MOF) nanoparticles. They combine the advantages of liposomes with an easy and efficient loading process. In this work, we present the successful synthesis of liposome-coated MOF nanoparticles via the fusion method. The resulting particles, once loaded, show no premature leakage and an efficient release. Their successful loading with both single and multiple drugs at the same time makes them an interesting candidate for use in combination therapy.

Ascorbyl Tetraisopalmitate Inclusion into Υ-Cyclodextrin and Mesoporous SBA-15: Preparation, Characterization and In Vitro Release Study

Ascorbic acid or vitamin C is a strong antioxidant widely used in cosmetic and food fields. This vitamin is very unstable and rapidly undergoes degradation. In order to solve this problem and to obtain a stable ascorbic acid, Nikkol Group has developed ascorbyltetraisopalmitate (VC-IP). This raw material is an oil phase, already well-known and employed in the cosmetic market. The objective of this study is to obtain VC-IP in micro-powder form, in order to produce a new raw material that is easily dispersible in oil and water phases and useful for make-up and color cosmetic applications. Various types of drug carriers were studied and considered in order to support VC-IP and obtain the conversion in powder. Υ-cyclodextrin and mesoporous silica SBA-15 were chosen as the best candidates. A white powder of supported VC-IP was obtained with each carrier (VC-IP@cyclodextrin, VC-IP@SBA-15). The systems underwent physicochemical characterization and in vitro release tests were carried out. Based on the conducted study, it can be concluded that by supporting VC-IP on Υ-cyclodextrin and SBA-15, it is feasible to obtain a new raw material in powder form. The two carriers possess different release profiles, adding the possibility to finely tune the release of the active component in smart formulations.

Stimuli-responsive delivery vehicles based on mesoporous silica nanoparticles: recent advances and challenges.

In the past decade, stimuli-responsive drug delivery vehicles based on surface-functionalized mesoporous silica nanoparticles (MSNs) have attracted intense interest as a new type of drug carrier. These intelligent drug delivery systems have been demonstrated to enable precise drug release into highly specified targets and exhibit nearly "zero premature release" in systemic circulation. It is expected that an in-depth understanding of the basic mechanisms of the MSN-based stimuli-responsive drug delivery systems (DDSs) would further contribute to this breakthrough field of nanomedicine. In this review, the recent advances in the development of stimuli-responsive systems based on MSNs are summarized and discussed, including single stimuli-responsive DDSs, dual stimuli-responsive DDSs and multi stimuli-responsive DDSs. The challenges for stimuli-responsive DDSs based on MSNs with regards to future translation into clinical use are also simply discussed.

Poly( N ‐isopropylacrylamide)/polyurethane core–sheath nanofibres by coaxial electrospinning for drug controlled release

A new type of drug carrier with thermo-sensitivity is reported. The system consisted of poly(N-isopropylacrylamide) (PNIPAAm) and polyurethane (PU) and two kinds of polymer were spun into core–sheath nanofibres without bead defects by coaxial electrospinning technique. Poor soluble nifedipine was used as a model drug to evaluate the release behaviour of drug from nanofibre carriers. Results showed that the diameter and diameter distribution of nanofibres varied with the ratios of the outer flow rate to the inner flow rate. PNIPAAm/PU core–sheath electrospun nanofibres maintained the thermo-sensitivity of PNIPAAm and the wettability of the electrospun nanofibres could be adjusted effectively by the change of the temperature. In-vitro release of nifedipine from nanofibre carriers showed that core–sheath electrospun nanofibres as the drug carrier could slow down the release rate of nifedipine compared with that of PNIPAAm/PU composite electrospun nanofibres, and then could effectively achieve the controlled release of nifedipine, avoiding the concentrated release of drug and reduce the toxicity.

Morphological study of efficacy of clarithromycin-loaded nanocarriers for treatment of biofilm infection disease.

In this study, we developed a drug delivery system (DDS) using polymeric nanocarriers for the treatment of biofilm infection disease. Clarithromycin (CAM)-encapsulated and chitosan (CS) modified polymeric nanoparticles (NPs) were prepared using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) (Sol) and poly-(DL-lactide-co-glycolide), respectively. To understand the availability of the prepared NPs, we made morphological observations of the antibacterial activity derived from the NPs toward the bacterial cells within the biofilm using scanning electron microscopy and transmission electron microscopy measurements. These results revealed different antibacterial activities for the two types of drug carriers. In the case of CAM-encapsulated+CS-modified Sol micelles treatment, NPs can exert their antibacterial activity not only by the surfactant, CAM and CS effects but also by intrusion into the bacterial cells. Thereby, CAM-encapsulated+CS-modified Sol micelles had a higher antibacterial activity. The morphological information is useful to design suitable NPs for the treatment against biofilm infections.

Dendrimer-like supramolecular nanovalves based on polypseudorotaxane and mesoporous silica-coated magnetic graphene oxide: a potential pH-sensitive anticancer drug carrier

In the present research, two types of drug carriers based on mesoporous silica-coated magnetic graphene oxide, Fe3O4@GO@mSiO2, were synthesised and the pH-responsive behaviour for doxorubicin release was investigated. One type of the carrier was dendrimer-like multi ethylene amine grafted on Fe3O4@GO@mSiO2 and the other was dendrimer-like supramolecular polypseudorotaxane. Herein, α-cyclodextrin was used in the structure of supramolecular nanoparticles as a gatekeeper to inhibit the drug from escaping at neutral pH (the pH of healthy tissue). The drug release profile showed that the supramolecular nanocarrier was more sensitive to the pH changes. The content of drug release was about 100% at pH 5.5 (endosomal pH) during 48 h; but it was zero at pH 7.4. Also, the dendrimer structure facilitated the triggered release of doxorubicin.

Active Drug Targeting of a Folate-Based Cyclodextrin–Doxorubicin Conjugate and the Cytotoxic Effect on Drug-Resistant Mammary Tumor Cells In Vitro

Active drug targeting is an effective therapeutic approach for the treatment of malignant cancers and novel types of drug carriers have been developed. In this study, we developed a cyclodextrin (CD)-based novel carrier-drug conjugate, called per-FOL-β-CD-ss-DOX, which has folic acid (FA) molecules at the end of primary hydroxyl groups of β-CD and a pH-cleavable spacer with an anticancer drug, doxorubicin (DOX), at the end of secondary hydroxyl groups. This per-FOL-β-CD-ss-DOX exhibited a significant cellular uptake as compared with the free DOX solution by EMT6/P cells, which activate the expression of folate receptor (FR). Cellular uptake of per-FOL-β-CD-ss-DOX was significantly inhibited in the presence of FA and was also inhibited at 4°C. The conjugate exhibited remarkable cytotoxic effects in EMT6/AR1 cells, which are resistant to DOX, whereas free DOX solution did not exhibit this effect. These results suggest that per-FOL-β-CD-ss-DOX can be taken up into cells via FR-related endocytosis and the cleaved DOX derived from it in endosomes could escape the efflux caused by P-glycoprotein, resulting in the cytotoxic effect. Therefore, the drug delivery by per-FOL-β-CD-ss-DOX may be a useful approach for drug delivery to FR-expressing cells such as drug-resistant malignant cancers.

Dual-sensitive and folate-conjugated mixed polymeric micelles for controlled and targeted drug delivery

For this study, we prepared a new type of drug carrier with the characteristics of stimuli-responsive transition and tumor-specific recognition through the co-assembly of two series of amphiphilic block copolymers, poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-methacryloyl caproic acid] and poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-(2-(methacrylamido)ethyl) folatic amide]. The pH-dependent thermal transition and the content of the targeting ligands of the mixed polymeric micelles are well correlated with the chemical structures and compositions of these two copolymers. Doxorubicin-loaded mixed polymeric micelles are stable at body temperature in the neutral condition for prolonged circulation in blood vessels, and demonstrated rapid drug release at acidic pH levels. The cumulative drug release profiles showed a relatively slow release at pH 7.4, and a quick release of 85% in 3h at pH 5.3. The cytotoxicity tests against FA-positive (HeLa) and FA-negative (HT-29) tumor cell lines suggest that this mixed polymeric micelle system has potential merits as a controlled and targeted drug delivery system.

Folate Receptor-Mediated Drug Targeting: A Possible Strategy for Nonfunctioning Pituitary Adenomas?

Clinically nonfunctioning pituitary adenomas (NFPAs) mostly arise from gonadotroph cells and account for about one-third of all pituitary tumors. Because they are not associated with hormone hypersecretion, these tumors are often diagnosed late when they are large and locally invasive. Consequently, the complete surgical removal of NFPAs is hard to achieve and they tend to recur. Medical treatment of NFPAs is still challenging because they are usually resistant to mainstay peptide receptor therapy with somatostatin (SRIF) analogs (octreotide and lanreotide) or dopamine agonists (bromocriptine and cabergoline). Indeed, although these agents may be useful in some cases to prevent residual tumor growth (1), their efficacy has not been confirmed in larger studies. Recently, SOM230 (pasireotide), a broad-range SRIF analog with affinity for SRIF receptor subtypes 1 to 3 and 5 (2) and BIM-23A760 (dopastatin), a chimeric agent interacting with both SRIF receptor and dopamine receptors were developed (3). However, NFPAs only partially respond to these compounds, at least in vitro (4, 5). After the discovery that NFPAs display overactivation of phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin pathway (6, 7), compounds inhibiting this signaling cascade at various levels have been tested against these tumors. The results are very promising, especially for dual inhibitors such as BEZ235 and XL765, which inhibit both mammalian target of rapamycin and the upstream phosphatidylinositol 3-kinase and exert a potent antiproliferative activity against primary human NFPA cells (8), rodent pituitary cell lines (9), and primary rat gonadotroph adenoma cells in vitro (10). In vivo studies are now required to prove or disprove the efficacy of these agents. Conventional chemotherapy has been one of the major medical advances of the last decades, but it is usually associated with poor specificity for the cancer cells and high toxicity to the normal cells. To overcome these limitations, it would be ideal to identify ways to deliver a biologically effective concentration of anticancer agents to the tumor tissues with very high specificity. To reach this ultimate goal, extensive efforts have been undertaken to develop tumor-selective drugs by conjugating therapeutic agents to hormones, antibodies, and vitamin derivatives. Among them, folic acid holds great promise as a tumor-homing agent (11). Folate (or folic acid) is an essential B vitamin, which plays a pivotal role in cell survival by participating in the biosynthesis of nucleic and amino acids. Folate is internalized into the cells via a low-affinity reduced folate carrier protein or via high-affinity folate receptors. The best studied isoform of these receptors is folate receptor(FR ), a cell surface glycosyl phosphatidylinositol-anchored glycoprotein that can internalize bound folates and folate-conjugated compounds via receptor-mediated endocytosis (12). Whereas FR has a very restricted expression pattern in normal tissues, it is expressed at a high level in various human cancers, particularly epithelial carcinomas, including nonmucinous ovarian carcinoma, cervical carcinomas, and testicular choriocarcinomas, and less frequently in breast, endometrial colon, and renal cell carcinomas (13, 14). Due to its selective expression in tumor but not normal cells, FR has become one of the most investigated cellular surface antigens for targeted delivery of a variety of molecules, including imaging agents, chemotherapeutic agents, oligodeoxynucleotides, and macromolecules. Various types of drug carriers have been conjugated to folate such as liposomes, lipid nanoparticles, polymeric nanoparticles, polymers, and micelles filled with the molecule that needs to be delivered (11). FR -targeted liposomal

Drug targeting with nano-sized carrier systems

This paper discusses the present status of, and future perspectives on, drug targeting through the bloodstream by describing the drug targeting concept, its methodologies, types of drug carriers, and recent clinical examples. This explanation and discussion is made from the viewpoint of possible correlations with studies on artificial organs, implants, and biomaterials. Two targeting methodologies (active and passive targeting), two targeting strategies (the magic bullet and the enhanced permeability and retention effect), and five types of drug carriers are explained. In addition, the clinical status of the five carrier systems is discussed.

癌治療とＤＤＳ 癌の標的治療のためのキャリア設計

Site-specific control of drug delivery to the tumor has been grately expected to achieve successful cancer chemotherapy by using carrier systems targeted to the tumor by controlling their in vivo physical and/or chemical interactions. For anticancer targeting systems, several types of drug carriers have been investigated. However, non-selective scavenging by the reticuloendothelial system is a serious problem even when carriers are monoclonal antibodies. Recently, the anticancer targeting systems are approched with the overall perspective of in vivo interactions of the targeted carrier with biocomponents including proteins, cells and organs as well as the binding affinities of the targeted carrier with cancer cells. The authors, herein, classify and explain the today's carrier systems for cancer chemotherapy into three categories : 1) Active targeting utilizing specific molecular recognition of antibodys or receptors, 2) Passive targeting achieved by controlling biodistribution of the carriers by regulating their pyhsical properties such as a size, hydrophilicity, charge, etc., and 3) Drug modulation using intelligent materials controlling drug biodistribution and/or drug bioactivity in response to external, physical stimuli such as temperature, light, magnetism, etc.. These systems are further developed by a conjunction of the systems resulting in amplification of the targeting efficacy. In order to achieve clinical application of these targeted carrier systems, interdisciplinary research of pharmaceutics, engineering and medicine must be required. Advanced science has been developing for design of the novel drug targeting system. In the future, progressive improvement of this area is expected to achieve effective cancer chemotherapy.