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Local drug delivery

Fauzia A Khan, Alan F Merry
The safety of anesthesia characteristic of high-income countries today is not matched in low-resource settings with poor infrastructure, shortages of anesthesia providers, essential drugs, equipment, and supplies. Health care is delivered through complex systems. Achieving sustainable widespread improvement globally will require an understanding of how to influence such systems. Health outcomes depend not only on a country's income, but also on how resources are allocated, and both vary substantially, between and within countries...
April 2018: Anesthesia and Analgesia
Andrea J Santamaría, Juan P Solano, Francisco D Benavides, James D Guest
Cell transplant-mediated tissue repair of the damaged spinal cord is being tested in several clinical trials. The current candidates are neural stem cells, stromal cells, and autologous Schwann cells (aSC). Due to their peripheral origin and limited penetration of astrocytic regions, aSC are transplanted intralesionally as compared to neural stem cells that are transplanted into intact spinal cord. Injections into either location can cause iatrogenic injury, and thus technical precision is important in the therapeutic risk-benefit equation...
2018: Methods in Molecular Biology
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Ling Gui Ning, En-Tang Kang, Yun Bing Wang, Xue Feng Hu, Li Qun Xu
Traditional use of antibiotics through injection or oral ingestion has many disadvantages, such as detrimental side effects in the host, less effectiveness, high and repeated doses, and development of drug resistance. For prevention and treatment of implant-associated infections, the continuous local delivery of antibiotics is required. Thus, there is a strong demand for the development of drug carrier systems to control the release of antibiotics in a moderate manner over an appropriate timescale. This review summarizes the carrier platforms used for the loading of antibiotics, and highlights their drug release behaviors as well as in vitro and in vivo antibacterial properties...
March 14, 2018: Current Pharmaceutical Design
Ming-Xing Zhang, Shan-Shan Hong, Qing-Qing Cai, Meng Zhang, Jun Chen, Xiao-Yan Zhang, Cong-Jian Xu
Ovarian cancer is the leading cause of cancer death among gynecological malignancies. The high mortality rate has not been significantly reduced despite advances in surgery and chemotherapy. Gene therapy shows therapeutic potential, but several key issues must be resolved before clinical application. To minimize toxicity in noncancerous tissues, tumor-specific ligands are conjugated to vectors to increase the selectivity of drug delivery. The expression pattern of follicle-stimulating hormone (FSH) receptor in normal and cancer tissues provides an opportunity for highly selective drug delivery in ovarian cancer...
November 2018: Drug Delivery
Xiaofeng Wang, Wei Wang, Wei Li, Zhiduo Niu, Qing Wang, Dianwen Zhang, Hui Li, Jincheng Wang
Local drug delivery systems have been proposed for the treatment of periodontitis, and Hylotelephium purpureum may be a suitable agent for use in such a system. The present study aimed to formulate a Hylotelephium purpureum gel (HPG) and evaluate the anti-inflammatory activity and antinociceptive effects of Hylotelephium purpureum and to assess the duration of action and efficacy of HPG in the treatment of experimental periodontitis in a KM mouse model. First, an acute toxicity study was performed, and secondly, xylene-induced mouse-ear edema, acetic acid-induced mouse peritoneal capillary permeability and carrageenan-induced hind-paw edema tests were used to investigate the anti-inflammatory activity of the gel...
April 2018: Biomedical Reports
Na Kong, Mei Deng, Xiu-Na Sun, Yi-Ding Chen, Xin-Bing Sui
Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL- ran -PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL- ran -PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL- ran -PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment...
2018: Frontiers in Pharmacology
Michelle L Ratay, Stephen C Balmert, Ethan J Bassin, Steven R Little
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation...
March 8, 2018: Acta Biomaterialia
Mónika Bakonyi, Attila Gácsi, Anita Kovács, Mária-Budai Szűcs, Szilvia Berkó, Erzsébet Csányi
The application of local anesthetics, usually administered by subcutaneous injection, is common in the course of diagnostic, therapeutic, and cosmetic dermatology procedures. The effective dermal delivery of lidocaine could offer a solution to many adverse effects caused by needle insertion, such as pain, local reactions or toxicity, and additionally, it avoids the disruption of anatomical landmarks. Therefore, novel dermal formulations of local anesthetics are needed to overcome the barrier function of the skin and provide sufficient and prolonged anesthesia...
March 6, 2018: Journal of Pharmaceutical and Biomedical Analysis
Pierre Maudens, Christian Alexander Seemayer, François Pfefferlé, Olivier Jordan, Eric Allémann
This study aimed to formulate nanocrystal-polymer particles containing the potent p38α/β MAPK inhibitor PH-797804 (PH-NPPs) and to test their extended-release properties over months in comparison to those of conventional PH microparticles for the intra-articular treatment of inflammatory and mechanistic murine models mirroring aspects of human osteoarthritis (OA). The steps of the study were (i) to formulate PH nanocrystals (wet milling), (ii) to encapsulate a high payload of PH nanocrystals in fluorescent particles (spray drying), (iii) to assess in vitro drug release, (iv) to evaluate PH-NPP toxicity to human OA synoviocytes (MTT test), (v) to investigate the in vivo bioactivity of the particles in mice in an inflammatory antigen-induced arthritis (AIA) model (using histology and RT-qPCR) and (vi) to investigate the in vivo bioactivity of the particles in the OA model obtained by mechanistic surgical destabilization of the medial meniscus (DMM) (using histology, micro-CT, and multiplex ELISA)...
March 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hiba Natsheh, Elka Touitou
The goal of this work was to investigate a new nasal carrier for enhanced drug delivery to brain, we call Phospholipid Magnesome. The system contains soft phospholipid vesicles, composed of phospholipid, water, propylene glycol, magnesium salt, and the mucoadhesive polymer, alginate. The carrier was characterized by various methods: electron microscopy, calorimetry, and dynamic light scattering. The ability of the carrier's vesicles to entrap various molecules was studied by CLSM and ultracentrifugation combined with HPLC quantification...
March 9, 2018: Drug Delivery and Translational Research
Arunima Pramanik, Rudra Narayan Sahoo, Ashirbad Nanda, Rajaram Mohapatra, Ranveer Singh, Subrata Mallick
PURPOSE: Kaolin can adhere to the mucosa and protect it by absorbing toxins, bacteria, and viruses. Ocular delivery and anti-inflammatory activity of dexamethasone hydrogel system could be advantageous after kaolin incorporation. METHODS: Hydroxypropyl methylcellulose (HPMC) films of dexamethasone have been prepared without and with kaolin by solvent casting method. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were utilized for evaluating thermal property, crystallinity, and morphology of the film preparations respectively...
March 9, 2018: Current Eye Research
Adolfo Marican, Fabián Avila-Salas, Oscar Valdés, Sergio Wehinger, Jorge Villaseñor, Natalia Fuentealba, Mauricio Arenas-Salinas, Yerko Argandoña, Verónica Carrasco-Sánchez, Esteban F Durán-Lara
This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs) as platforms for the sustained release of prednisone (PDN). Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD) was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA) was shown to be the best candidate for containing γ-CD...
March 7, 2018: Pharmaceutics
Zhigao Niu, Eleni Samaridou, Emilie Jaumain, Julie Coëne, Gabriela Ullio, Neha Shrestha, Josep Garcia, Matilde Durán-Lobato, Sulay Tovar, Manuel J Santander-Ortega, M Victoria Lozano, M Mar Arroyo-Jiménez, Rocío Ramos-Membrive, Iván Peñuelas, Aloïse Mabondzo, Véronique Préat, Meritxell Teixidó, Ernest Giralt, María José Alonso
The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer...
March 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Heni Rachmawati, Yang Aryani Arvin, Sukmadjaja Asyarie, Kusnandar Anggadiredja, Raymond Rubianto Tjandrawinata, Gert Storm
Bupivacaine HCl (1-butyl-2',6'-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9 h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects...
March 7, 2018: Drug Delivery and Translational Research
Haitao Li, Yunfei Teng, Xia Xu, Jianyong Liu
The most common tumors in children are infantile hemangiomas which could cause morbidity and severe complications. The development of novel alternative drugs to treat infantile hemangiomas is necessary, since Hemangeol is the only US Food and Drug Administration-approved drug for infantile hemangiomas. However, Hemangeol has several disadvantages, including a high frequency of administration and adverse effects. Rapamycin is a well‑established antiangiogenic drug, and we have previously developed rapamycin lipid polymer nanoparticles (R‑PLNPs) as a local sustained‑release drug delivery system to achieve controlled rapamycin release and to decrease the frequency of administration and side effects of rapamycin...
February 28, 2018: International Journal of Molecular Medicine
Yang Cao, Yuli Chen, Tao Yu, Yuan Guo, Fengqiu Liu, Yuanzhi Yao, Pan Li, Dong Wang, Zhigang Wang, Yu Chen, Haitao Ran
Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets...
2018: Theranostics
Dan Høgdall, Monika Lewinska, Jesper B Andersen
Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies...
March 2018: Trends in Cancer
Jae Hwan Jung, Bryce Chiang, Hans E Grossniklaus, Mark R Prausnitz
Treatment of many posterior-segment ocular indications would benefit from improved targeting of drug delivery to the back of the eye. Here, we propose the use of iontophoresis to direct delivery of negatively charged nanoparticles through the suprachoroidal space (SCS) toward the posterior pole of the eye. Injection of nanoparticles into the SCS of the rabbit eye ex vivo without iontophoresis led to a nanoparticle distribution mostly localized at the site of injection near the limbus and <15% of nanoparticles delivered to the most posterior region of SCS (>9 mm from the limbus)...
March 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Francesca Citossi, Thomas Smith, Jong Bong Lee, Joel Segal, Pavel Gershkovich, Michael John Stocks, Tracey D Bradshaw, Barrie Kellam, Maria Marlow
Low molecular weight gelators (LMWGs) of chemotherapeutic drugs represent a valid alternative to the existing poly-mer-based formulations used for targeted delivery of anticancer drugs. Herein we report the design and development of novel self-assembling gelators of the antitumour benzothiazole 5F 203 (1). Two different types of derivatives of 1 were synthesized, formed by an amide (2) and a carbamate (3a-3d) linker, respectively, which showed potent in vitro anti-tumour activity against MCF-7 mammary and IGROV-1 ovarian carcinoma cells...
March 5, 2018: Molecular Pharmaceutics
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