Safe Drug Delivery System Research Articles

Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release.

Background and purposeGlioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier.MethodsThe core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism.ResultsTQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer–Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ.ConclusionUse of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.

Study of biodistribution and systemic toxicity of glucose functionalized SPIO/DOX micelles

The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r2*) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system.

Mucoadhesive In Situ Gelling Liquid Crystalline Precursor System to Improve the Vaginal Administration of Drugs.

The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems.

Hollow Microcapsules with Ulcerative Colitis Therapeutic Effects Made of Multifunctional Turkish Galls Extraction.

Ulcerative colitis (UC) has been listed as one of the refractory diseases of modern society by the World Health Organization. Our previous studies found that Turkish galls Gallotannins (TGTs) have a significant effect on anti-UC. Here, TGTs were extracted using a simple method and TGTs-FeIII microcapsules were prepared by a self-assembly technique. Microcapsules were characterized by liquid chromatography-mass spectrometry, scanning electron microscopy, and so forth. The results verified that hollow spheres of TGTs-FeIII microcapsules were successfully prepared. It is interesting that microcapsules were more likely to accumulate on the inflammatory surface from ex vivo and in vivo adhesion experiments, and effectively alleviate UC symptoms. This study will provide valuable insight into the development of safe and efficient drug delivery system platforms for further biomedical usages.

Tissue Interlocking Dissolving Microneedles for Accurate and Efficient Transdermal Delivery of Biomolecules

The interest in safe and efficient transdermal drug delivery systems has been increasing in recent decades. In light of that, polymeric dissolving microneedles (DMNs) were developed as an ideal platform capable of delivering micro- and macro-biomolecules across the skin in a minimally invasive manner. A vast majority of studies, however, suggest that the shape of DMNs, as well as the elastic properties of skin, affects the delivery efficiency of materials encapsulated within DMNs. Likewise, in dynamic tissues, DMNs would easily distend from the skin, leading to inefficient delivery of encapsulated agents. Thus, herein, to improve delivery efficiency of DMN encapsulated agents, a novel hyaluronic acid backbone-based tissue interlocking DMN (TI-DMN) is developed. TI-DMN is simple to fabricate and significantly improves the transdermal delivery efficiency of encapsulated materials compared with traditional DMNs. The enhanced tissue interlocking feature of TI-DMN is achieved through its sharp tip, wide body, and narrow neck geometry. This paper demonstrates that TI-DMN would serve as an attractive transdermal delivery platform to enhance penetration and delivery efficiency of a wide range of biomolecules into the body.

In vivo biocompatibility, pharmacokinetics, antitumor efficacy, and hypersensitivity evaluation of ionic liquid-mediated paclitaxel formulations.

In order to prevent common hypersensitivity reactions to paclitaxel injections (Taxol), we previously reported an ionic liquid-mediated paclitaxel (IL-PTX) formulation with small particle size and narrow size distribution. The preliminary work showed high PTX solubility in the IL, and the formulation demonstrated similar antitumor activity to Taxol, while inducing a smaller hypersensitivity effect in in vitro cell experiments. In this study, the stability of the IL-PTX formulation was monitored by quantitative HPLC analysis, which showed that IL-PTX was more stable at 4 °C than at room temperature. The in vivo study showed that the IL-PTX formulation could be used in a therapeutic application as a biocompatible component of a drug delivery system. To assess the in-vivo biocompatibility, IL or IL-mediated formulations were administered intravenously by maintaining physiological buffered conditions (neutral pH and isotonic salt concentration). From in vivo pharmacokinetics data, the IL-PTX formulation was found to have a similar systemic circulation time and slower elimination rate compared to cremophor EL mediated paclitaxel (CrEL-PTX). Furthermore, in vivo antitumor and hypersensitivity experiments in C57BL/6 mice revealed that IL-PTX had similar antitumor activity to CrEL-PTX, but a significantly smaller hypersensitivity effect compared with CrEL-PTX. Therefore, the IL-mediated formulation has potential to be an effective and safe drug delivery system for PTX.

Incidence of postoperative atrial fibrillation in transdermal β-blocker patch users is lower than that in oral β-blocker users after cardiac and/or thoracic aortic surgery.

Postoperative atrial fibrillation (POAF) after open heart surgery is associated with a high risk of mortality and morbidity. Although oral β-blockers are usually recommended to prevent POAF, the efficacy of a transdermal β-blocker patch in preventing POAF is unclear. We compared the incidence of POAF between users of oral and transdermal bisoprolol. We investigated 108 patients who underwent cardiac and/or thoracic aortic surgery between April 2016 and February 2018. We compared perioperative clinical and hemodynamic variables between 49 patients treated with a transdermal bisoprolol patch and 59 patients treated with an oral bisoprolol fumarate. POAF occurred in 24% of patients in the transdermal and in 46% of patients in the oral bisoprolol groups (p = 0.027). No intergroup difference was observed in in-hospital mortality, perioperative blood pressures and heart rates, and other morbidities. Multivariable logistic regression analysis revealed that the use of transdermal bisoprolol was independently associated with a lower rate of POAF (odds ratio 0.21, 95% confidence interval 0.05-0.84, p = 0.027). A transdermal bisoprolol patch is an effective and safe β-blocker drug delivery system. The incidence of POAF in this group was lower than that in users of oral bisoprolol.

Surface-modified PLGA nanoparticles with PEG/LA-chitosan for targeted delivery of arsenic trioxide for liver cancer treatment: Inhibition effects enhanced and side effects reduced

Arsenic trioxide (As2O3), an effective drug for leukemia, is limited to be used for solid tumor treatment due to its high side effects. In this study, polyethylene glycol (PEG) and lactobionic acid (LA) modified chitosan (PLC) was synthesized and was used to coat poly(lactide-co-glycolide) (PLGA) nanoparticles for encapsulation and targeted release of As2O3 in liver cancer treatment. The As2O3-loaded PLGA/PLC nanoparticles (As2O3-PLGA/PLC NPs) were fabricated through double emulsion-solvent evaporation method and were optimized by orthogonal tests. As2O3-PLGA/PLC NPs presented suitable physical stability, positive charge, high encapsulation efficiency and drug loading, and good biocompatibility. As expected, the NPs can quickly release enough dose of As2O3 in a short time and then sustain the drug concentration. The As2O3-PLGA/PLC NPs showed effective inhibition of SMMC-7721 cells while having lower cytotoxicity against normal human liver cells (LO2 cells). Furthermore, In vivo study showed that the NPs did not present toxic effects on kidney and liver, but showed relatively high growth inhibition effect on liver tumor. Therefore, this PLGA/PLC NPs could be an effective and safe drug delivery system for liver cancer chemotherapy.

Harnessing Exosomes for the Development of Brain Drug Delivery Systems.

Brain drug delivery is one of the most important bottlenecks in the development of drugs for the central nervous system. Cumulative evidence has emerged that extracellular vesicles (EVs) play a key role in intercellular communication. Exosomes, a subgroup of EVs, have received the most attention due to their capability in mediating the horizontal transfer of their bioactive inclusions to neighboring and distant cells, and thus specifically regulating the physiological and pathological functions of the recipient cells. This native and unique signaling mechanism confers exosomes with great potential to be developed into an effective, precise, and safe drug delivery system. Here, we provide an overview into the challenges of brain drug delivery and the function of exosomes in the brain under physiological and pathological conditions, and discuss how these natural vesicles could be harnessed for brain drug delivery and for the therapy of brain diseases.

Nanoemulsions for "Nose-to-Brain" Drug Delivery.

The blood–brain barrier (BBB) plays a fundamental role in protecting the brain from toxic substances and therefore also controls and restricts the entry of therapeutic agents. The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB. Through the nasal route, the drug can access the brain directly along the trigeminal and olfactory nerves, which are located in the upper part of the nasal cavity. Nanoemulsions are formulations belonging to the field of nanomedicine. They consist of emulsions (commonly oil in water) stabilized by one or more surfactants—and eventually co-surfactants—delivered in droplets of small dimensions (sizes of 100–300 nm or less) with a high surface area. A mucoadhesive polymer such as chitosan can be added to the formulation to impair rapid nasal clearance. Nanoemulsions represent promising formulations to deliver drugs directly into the brain through the intranasal route. Therefore, they can be used as a possible alternative to oral administration, avoiding problems such as low solubility in water, poor bioavailability, enzymatic degradation and slow onset of action. This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

Curcumin- and Fish Oil-Loaded Spongosome and Cubosome Nanoparticles with Neuroprotective Potential against H2O2-Induced Oxidative Stress in Differentiated Human SH-SY5Y Cells

Many phytochemical antioxidant compounds, including curcumin (CU), are water-insoluble and thus require delivery carriers in order to increase their bioavailability for in vivo applications. Oxidative stress-related apoptosis is a common cause for the neuronal loss in the progression of neurodegenerative diseases. Lipid nanoparticles (NPs) with internal self-assembled liquid crystalline structures present strong interest as safe drug delivery systems for neuronal regeneration through combination therapies. Here, we report spongosome and cubosome lipid NPs, which co-encapsulate CU and fish oil (FO), rich in ω-3 polyunsaturated fatty acids. The performed structural investigation by synchrotron small-angle X-ray scattering evidenced the liquid crystalline organization of the self-assembled NPs. The encapsulation efficiency for CU in the lipid nanocarriers was found to be higher as compared to that reported for polymer-based carriers. The cytotoxicity of the blank and antioxidant-loaded nanocarriers was negli...

Pharmacists in Critical Care.

The beginnings of caring for critically ill patients date back to Florence Nightingale's work during the Crimean War in 1854, but the subspecialty of critical care medicine is relatively young. The first US multidisciplinary intensive care unit (ICU) was established in 1958, and the American Board of Medical Subspecialties first recognized the subspecialty of critical care medicine in 1986. Critical care pharmacy services began around the 1970s, growing in the intervening 40 years to become one of the largest practice areas for clinical pharmacists, with its own section in the SCCM, the largest international professional organization in the field. During the next decade, pharmacy services expanded to various ICU settings (both adult and pediatric), the operating room, and the emergency department. In these settings, pharmacists established clinical practices consisting of therapeutic drug monitoring, nutrition support, and participation in patient care rounds. Pharmacists also developed efficient and safe drug delivery systems with the evolution of critical care pharmacy satellites and other innovative programs. In the 1980s, critical care pharmacists designed specialized training programs and increased participation in critical care organizations. The number of critical care residencies and fellowships doubled between the early 1980s and the late 1990s. Standards for critical care residency were developed, and directories of residencies and fellowships were published. In 1989, the Clinical Pharmacy and Pharmacology Section was formed within the Society of Critical Care Medicine, the largest international, multidisciplinary, multispecialty critical care organization. This recognition acknowledged that pharmacists are necessary and valuable members of the physician-led multidisciplinary team. The Society of Critical Care Medicine Guidelines for Critical Care Services and Personnel deem that pharmacists are essential for the delivery of quality care to critically ill patients. These guidelines recommend that a pharmacist monitor drug regimen for dosing, adverse reactions, drug-drug interactions, and cost optimization for all hospitals providing critical care services. The guidelines also advocate that a specialized, decentralized pharmacist provide expertise in nutrition support, cardiorespiratory resuscitation, and clinical research in academic medical centers providing comprehensive critical care.

A novel nitroalkene-α-tocopherol analogue inhibits inflammation and ameliorates atherosclerosis in Apo E knockout mice.

Atherosclerosis is characterized by chronic low-grade inflammation with concomitant lipid accumulation in the arterial wall. Anti-inflammatory and anti-atherogenic properties have been described for a novel class of endogenous nitroalkenes (nitrated-unsaturated fatty acids), formed during inflammation and digestion/absorption processes. The lipid-associated antioxidant α-tocopherol is transported systemically by LDL particles including to the atheroma lesions. To capitalize on the overlapping and complementary salutary properties of endogenous nitroalkenes and α-tocopherol, we designed and synthesized a novel nitroalkene-α-tocopherol analogue (NATOH) to address chronic inflammation and atherosclerosis, particularly at the lesion sites. We synthesized NATOH, determined its electrophilicity and antioxidant capacity and studied its effects over pro-inflammatory and cytoprotective pathways in macrophages in vitro. Moreover, we demonstrated its incorporation into lipoproteins and tissue both in vitro and in vivo, and determined its effect on atherosclerosis and inflammatory responses in vivo using the Apo E knockout mice model. NATOH exhibited similar antioxidant capacity to α-tocopherol and, due to the presence of the nitroalkenyl group, like endogenous nitroalkenes, it exerted electrophilic reactivity. NATOH was incorporated in vivo into the VLDL/LDL lipoproteins particles to reach the atheroma lesions. Furthermore, oral administration of NATOH down-regulated NF-κB-dependent expression of pro-inflammatory markers (including IL-1β and adhesion molecules) and ameliorated atherosclerosis in Apo E knockout mice. In toto, the data demonstrate a novel pharmacological strategy for the prevention of atherosclerosis based on a creative, natural and safe drug delivery system of a non-conventional anti-inflammatory compound (NATOH) with significant potential for clinical application.

Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations.

Hot melt extrusion (HME), a technology which mixing the advantages of solid dispersion technology and mechanical preparation, is accepted in varied applications in pharmaceutical formulations. When combined with other techniques, such as nanotechnique, three-dimensional printing, and co-extrusion, HME becomes much more multifunctional in the application of drug delivery. While in most cases, polymers employed in HME are responsible for the final property of products. The process of HME together with the selection of materials employed in HME were described briefly. In addition, the applications of HME in drug delivery and its currently status in the pharmaceutical field were also included. Some commercial products produced by HME have met the approval of FDA, indicating the commercial viability of this technique. Although showing great potential in pharmaceutical manufacturing, HME is still challenged by high temperature, shear force, and high input energy. Development of equipment, modifying the parameters, and optimization of polymeric formulations are needed for a safe, effective, and multifunctional hot melt extrusion drug delivery system. Also, wider range of combinations between HME and other techniques may provide guideline for developing multiple applications in drug delivery.

DISSECTING CYFIP1 AND CYFIP2 CONTRIBUTIONS TO COMPULSIVE-LIKE BEHAVIOR AND BINGE EATING IN MICE: IMPLICATIONS FOR EATING DISORDERS AND NEURODEVELOPMENTAL DISORDERS WITH HYPERPHAGIA

Combination therapies for cancer have attracted great attention recently due to their synergistic effects to improve the therapeutic efficacy. In order to concurrently deliver dual or multiple drugs within solid tumor and exert their therapeutic effect, developing an intelligent and safe drug delivery system is highly expected. In this work, we synthesized a series of dual thermo- and pH-responsive copolymers containing hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) that was copolymerized with a β-alanine-functionalized monomer (βA). Both thermo and pH-response in a suitable window for physiological environment can be achieved via adjusting the ratios of NIPAAm and acidic moieties. The chemotherapeutic drug doxorubicin (DOX) and photosensitizer (meso-tetraphenylchlorin, m-TPC) have been simultaneously encapsulated in PCL-b-P(NIPAAm-co-βA) polymeric micelles with hydrodynamic diameters around 231–269 nm. The in vitro release studies demonstrated the increased drug release at acidic pH 6. The cell viability treated with dual drug-loaded micelles showed improved therapeutic efficiency under light irradiation, indicating combined effect of DOX and m-TPC has potential as dual-modality for cancer treatment.

Molecular simulation and in vitro evaluation of chitosan nanoparticles as drug delivery systems for the controlled release of anticancer drug cytarabine against solid tumours.

The present work is an attempt to integrate the molecular simulation studies with in vitro cytotoxicity of cytarabine-loaded chitosan nanoparticles and exploring the potential of this formulation as therapeutics for treating solid tumours. The molecular simulation was performed using GROMACS v5.4 in which, chitosan polymer (CHT; six molecules) was used to study the encapsulation and release of a single molecule of cytarabine. Root Mean Square Deviation (RMSD) of the Cα atom of cytarabine (CBR) molecule shows that CBR starts to diffuse out of the CHT polymer binding pocket around 10.2ns, indicated by increased fluctuation of RMSD at pH 6.4, while the drug diffusion is delayed at pH 7.4 and starts diffusing around 17.5ns. Cytarabine-loaded chitosan nanoparticles (CCNP), prepared by ionic gelation method were characterized for encapsulation efficiency, particle size and morphology, zeta potential, crystallinity and drug release profile at pH 6.4 and 7.4. CCNPs showed 64% encapsulation efficiency with an average diameter of 100nm and zeta potential of + 53.9mV. It was found that cytarabine existed in amorphous state in nanoformulation. In vitro release studies showed 70% cytarabine was released from the chitosan-based nanoformulation release at pH 6.4, which coincides with the pH of tumour microenvironment. Cytotoxicity against breast cancer cell line (MCF 7) was higher for nanoformulation compared to free cytarabine. Haemocompatibility studies showed that chitosan-based nanoformulation is safe, biocompatible and nonhaemolytic in nature; hence, can be used as a safe drug delivery system. Taken together, our study suggests that chitosan nanoformulation would be an effective strategy for the pH-dependent release of cytarabine against solid tumours and might impart better therapeutic efficiency.

Fabrication and evaluation of a γ-PGA-based self-assembly transferrin receptor-targeting anticancer drug carrier.

Backgroundcis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects.Materials and methodsIn this study, we constructed a safe and efficient anticancer drug delivery system PGA–Asp–maleimide–cisplatin–peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker. The size of PAMCP was identified by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Fluorescence microscopy and flow cytometry methods were used to detect the cell targeting ability in vitro. The MTT assay was used to detect targeted toxicity in vitro. The in vivo acute toxicity was tested in Kun Ming (KM) mice. The tumor suppression activity and drug distribution was analyzed in nude mice bearing with HeLa tumor cells.ResultsThe nano-size was 110±28 nm detected with TEM and 89±18 nm detected with DLS, respectively. Fluorescence microscopy and flow cytometry methods indicated that PAMCP possessed excellent cell targeting ability in vitro. The MTT assay suggested that PAMCP was excellent for targeted toxicity. The acute in vivo toxicity study revealed that the body mass index and serum index in the PAMCP-treated group were superior to those in the CDDP-treated group (P<0.001), and no obvious differences were detected on comparing with the PBS- or PGA–Asp–maleimide–P8 (PAMP)-treated groups. PAMCP reduced the toxicity of CDDP, suppressed tumor cell growth, and achieved efficient anti-tumor effects in vivo. After PAMCP treatment, the toxicity of CDDP was reduced and tumor growth was more remarkably inhibited compared with the free CDDP treatment group (P<0.01). Much stronger (5–10 folds) fluorescence intensity in tumor tissue was detected compared with the irrelevant-peptide group for drug distribution analysis detected with the frozen section approach.ConclusionOur data highlighted that PAMCP reduced the side effects of CDDP and exhibited stronger anti-tumor effects. Therefore, PAMCP presented the potential to be a safe and effective anticancer pharmaceutical formulation for future clinical applications.

Folate-targeted nanostructured chitosan/chondroitin sulfate complex carriers for enhanced delivery of bortezomib to colorectal cancer cells

Folate-targeting self-assembled nanoparticles (NPs) using biocompatible and biodegradable natural polymers chitosan (Cs) and chondroitin sulfate (Chs) were developed to address the major challenge in cancer treatment, the selective delivery of nanoparticles to the target site. In this study, we successfully incorporated a hydrophobic drug, bortezomib (Bor), into folic acid (FA)-conjugated Cs/Chs self-assembled NPs (Bor/Cs/Chs-FA) for colorectal cancer therapy. The particle size and polydispersity index of Bor/Cs/Chs-FA were ∼196.5 ± 1.2 nm and ∼0.21 ± 0.5, respectively. A pH-dependent release profile was observed, facilitating cancer cell-targeted drug release under an acidic tumor microenvironment. Moreover, in vitro data revealed enhanced cellular uptake and apoptosis in folate receptor-expressing colorectal cancer cells (HCT-116 and HT-29) as compared to that in lung cancer cells (A549), which do not express folate receptors. Furthermore, intravenous administration of Bor/Cs/Chs-FA in a HCT-116 bearing xenograft mouse model showed that the NPs were a safe and effective drug delivery system. The results suggest that folate-targeted nanoparticle can be effectively applied for efficient chemotherapy of colorectal cancer.

Development of efficient and safe drug delivery system with liposomes for clinical application ： 11&lt;sup&gt;th&lt;/sup&gt; Mizushima Award, Japan Society of DDS

Development of efficient and safe drug delivery system with liposomes for clinical application ： 11&lt;sup&gt;th&lt;/sup&gt; Mizushima Award, Japan Society of DDS

Hyaluronic acid-containing ethosomes as a potential carrier for transdermal drug delivery.

A hyaluronic acid-containing ethosomes (HA-ES) as the transdermal drug delivery system was prepared in this work, and rhodamine B (RB) was used as a model drug to be encapsulated. The obtained HA-ES-RB was then characterized by the surface morphology, entrapment efficiency, drug loading and the stability. Results showed that the prepared HA-ES-RB was spherical and showed good dispersion as well as the stability, with a particle size of below 100 nm. The skin permeation experiments were carried out in vitro with the Franz diffusion cells and the rat dorsal skins were used. It was found that the penetration effect of HA-ES-RB was much better than that of ES-RB. The fluorescence microscopy image showed that HA-ES-RB penetrated into the deepest dermis. The excellent transdermic drug delivery effect of HA-ES-RB maybe attributed from its smaller size, hydration of hyaluronic acid as well as greater potential targeting to skin and skin appendages of liposomal carriers. Moreover, the HA-ES delivery system showed non-cytotoxicity to normal cells, indicating a good biocompatibility. This work provded a hyaluronic acid-containing ethosomes which can offer a quick, high efficient, safe and self-administered transdermal drug delivery system.