首页期刊导航|European journal of pharmaceutical sciences
期刊信息/Journal information
European journal of pharmaceutical sciences
Elsevier
European journal of pharmaceutical sciences

Elsevier

0928-0987

European journal of pharmaceutical sciences/Journal European journal of pharmaceutical sciencesSCIICCCRISTP
正式出版
收录年代

    Nanocarriers Mediated Cutaneous Drug Delivery

    Gungor, SevgiKahraman, Emine
    12页
    查看更多>>摘要：The cutaneous drug delivery represents an attractive option for the management of skin diseases. However, the skin has a very complex morphological structure, although the skin barrier is disrupted in some of dermatological diseases. Therefore, to safely overcome the skin barrier and to deliver drugs across the skin efficiently is still remain as a challenge in the management of dermatological diseases. The nanocarrier mediated cutaneous delivery appears to offer a hope to provide targeting potential of the drugs into specific sites of the skin with minimizing side effects. This review highlights the human structure and diseased skin barrier, and possible therapeutic outcomes of nanocarrier based drug delivery in the treatment of skin diseases due to their skin transport and follicular targeting mechanisms, and summarizes recent studies in which polymer, lipid and surfactant based nanocarriers of drugs used in the skin diseases.
      原文链接:
    • NSTL
    • Elsevier

    EGFR-targeting antitumor therapy: Neuregulins or antibodies?

    de Lavera, IsabelMerkling, Patrick J.Oliva, Jose M.Sayagues, Maria J....
    10页
    查看更多>>摘要：Malignancies such as lung, breast and pancreatic carcinomas are associated with increased expression of the epidermal growth factor receptor, EGFR, and its role in the pathogenesis and progression of tumors has made this receptor a prime target in the development of antitumor therapies. In therapies targeting EGFR, the development of resistance owing to mutations and single nucleotide polymorphisms, and the expression of the receptor ligands themselves are very serious issues. In this work, both the ligand neuregulin and a bispecific antibody fragment to EGFR are conjugated separately or together to the same drug-delivery system to find the most promising candidate. Camptothecin is used as a model chemotherapeutic drug and superparamagnetic iron oxide nanoparticles as a delivery system. Results show that the lowest LD50 is achieved by formulations conjugated to both the antibody and the ligand, demonstrating a synergy. Additionally, the ligand location in the nucleus favors the antitumor activity of Camptothecin. The high loading capacity and efficiency convert these systems into a good alternative for administering Camptothecin, a drug whose use is otherwise severely limited by its chemical instability and poor solubility. Our choice of targeting agents allows treating tumors that express ErbB2 (Her2+ tumors) as well as Her2- tumors expressing EGFR.
      原文链接:
    • NSTL
    • Elsevier

    Prediction of plasma profiles of a weakly basic drug after administration of omeprazole using PBPK modeling

    Segregur, DomagojMann, JamesMoir, AndreaKarlsson, Eva M....
    9页
    查看更多>>摘要：Background: Oral medicines must release the drug appropriately in the GI tract in order to assure adequate and reproducible absorption. Disease states and co-administration of drugs may alter GI physiology and therefore the release profile of the drug. Acid-reducing agents (ARAs), especially proton pump inhibitors (PPIs), are frequently co-administered during various therapies. As orally administered drugs are frequently poorly soluble weak bases, PPI co-administration raises the risk of pH-induced drug-drug interactions (DDIs) and the potential for changes in the therapeutic outcome.
      原文链接:
    • NSTL
    • Elsevier

    Photostability studies of GarKS peptides for topical formulation development

    Diep, Dzung B.Tonnesen, Hanne HjorthThapa, Raj KumarWinther-Larsen, Hanne Cecilie...
    8页
    查看更多>>摘要：There is a growing interest in the use of antimicrobial peptides (AMPs) as potent alternatives for conventional antibiotics, especially in chronic infected wounds. The development of a suitable topical formulation requires a thorough assessment of the photostability profiles of AMPs. In this study, we sought to investigate the photostability of novel Garvicin KS (GarKS; composed of three peptides GakA, GakB, and GakC) peptides either as an individual peptide or in combinations. The photostability of the aqueous peptide solution was determined using Suntest (indoor and outdoor conditions). Furthermore, the antimicrobial efficacy of the peptides was evaluated following UVA irradiations. Photodegradation of the peptides under indoor and outdoor conditions followed first-order kinetics. Individual peptides (GakA, GakB, and GakC) were more prone to photodegradation as compared to combination peptides (GakA+GakB, GakB+GakC, and GakA+GakC) both under indoor and outdoor conditions where the GakA+GakB combination was the most photostable. A combination of GakA+GakB+GakC enhanced photostability under indoor conditions but was reduced under outdoor conditions. A combination of three peptides with an antioxidant (glutathione) or superoxide/hydrogen peroxide scavenger (trehalose) enhanced the photostability of peptides with the highest stability achieved at a peptide:photostabilizer molar ratio of 1:0.8 for glutathione. A nominal increase in the MIC value for the peptide combinations as opposed to a larger increase for individual peptides further supports the photostability effects of combination peptides following UVA irradiations. These results suggest that the GakA+GakB or GakA+GakB+GakC combinations exhibited the highest photostability with excellent antimicrobial efficacy deemed suitable for the development of a potent AMP formulation for topical applications.
      原文链接:
    • NSTL
    • Elsevier

    Preparation and Characterization of Protein-loaded PFC Nanoemulsions for the Treatment of Heart Diseases by Pulmonary Administration

    Zhu, LidongQuan, XiaoyuLiu, ZhiweiZhang, Hao...
    12页
    查看更多>>摘要：In the treatment of heart disease, strategies for the targeted delivery of protein therapeutics to the heart by inhalation are still immature. Perfluorocarbons (PFCs) are inert chemicals with good biocompatibility, and unique physico-chemical properties that have recently led to their applications in numerous fields. In this study, we combined the advantages of protein-phospholipid complexes and PFC emulsions and then synthesized protein-loaded PFC nanoemulsions (PNEs) to test whether, after inhalation, these nanoemulsions could deliver therapeutic proteins to the heart. After preparing protein-phospholipid complexes by lyophilization, we obtained PNEs by extrusion. The particle size and surface charge of PNEs were about 140 nm and-50 mV, respectively. In vitro results showed that the PNEs had a fine particle fraction of 35% and exhibited sustained protein release. Translocation studies were done using three types of pulmonary epithelial cells, and similar to 7% translocation was observed in the Calu-3 cell line. Further, they were easily absorbed by cells and had therapeutic effects in culture. In vivo results showed that the PNEs successfully delivered proteins to the myocardial tissue of rats and reduced ischemic myocardial injury caused by acute myocardial infarction (AMI). This study suggests that inhalation of PNEs is a new potential strategy to deliver proteins to cardiac tissues for treating heart diseases.
      原文链接:
    • NSTL
    • Elsevier

    Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats

    Celik-Tekeli, MerveCelebi, NevinTekeli, M. YasinAktas, Yesim...
    7页
    查看更多>>摘要：The objective of this study is to develop a new self-nanoemulsifying system containing exendin-4 with or without enzyme inhibitor chymostatin and to evaluate the effects of oral administration of exendin-4 and exendin-4/chymostatin loaded self nanoemulsifying system on plasma exendin-4, plasma insulin, blood glucose levels and to compare with the oral and subcutaneous administration of exendin-4 in non-diabetic and streptozotocin-induced type 2 diabetic rats. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying system containing ethyl oleate as the oil phase, Cremophor EL (R)/Labrasol (R) as the surfactants and propylene glycol as the co-solvent were prepared. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4 loaded self-nanoemulsifying system were found as 24.28 +/- 0.43 nm, 0.17 +/- 0.01, -1.28 +/- 3.61 mV, 79.60 +/- 3.30 m.Pas, respectively. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4/chymostatin loaded self-nanoemulsifying system were found as 20.25 +/- 0.35 nm, 0.11 +/- 0.02, -1.85 +/- 2.49 mV, 100.02 +/- 7.65 m.Pas, respectively according to our previous study. In the present study, we focused on long-term physical stability studies, pharmacokinetic studies and pharmacodynamic studies of prepared self-nanoemulsifying systems. According to the long-term physical stability data, exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems were found stable both at 5 degrees C +/- 3 degrees C and at 25 degrees C +/- 60% RH for 12 months. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems increased AUC and C-max values in non-diabetic rats compared to the oral exendin-4 solution. In diabetic rats, exendin-4/chymostatin loaded self nanoemulsifying systems increased C-max values compared to the exendin-4 solution. Exendin-4/chymostatin loaded self-nanoemulsifying system decreased inter-subject variability compared to commercial Byetta (R). At 30th minute after administration of exendin-4 loaded self-nanoemulsifying system, exendin-4/chymostatin loaded self nanoemulsifying system and Byetta (R), blood glucose levels decreased to 23%, 25%, 29%, respectively. It has been shown that pharmacodynamic response is close to Byetta (R) with exendin-4/chymostatin self-nanoemulsifying system oral administration. In conclusion, a self nanoemulsifying system was found to be a suitable carrier system, and the combination with enzyme inhibitor chymostatin is thought to be promising for oral delivery of exendin-4.
      原文链接:
    • NSTL
    • Elsevier

    Quality-by-design in hot melt extrusion based amorphous solid dispersions: An industrial perspective on product development

    Butreddy, ArunBandari, SureshRepka, Michael A.
    19页
    查看更多>>摘要：An industrially feasible approach to overcome the solubility and bioavailability limitations of poorly soluble active pharmaceutical ingredients is the development of amorphous solid dispersions (ASDs) using hot-melt extrusion (HME) technique. The application of Quality by Design (QbD) had a profound impact on the development of HME-based ASDs. The formulation and process optimization of ASDs manufactured via HME techniques require an understanding of critical quality attributes, critical material attributes, critical process parameters, risk assessment tools, and experimental designs. The knowledge gained from each of these QbD elements helps ensure the consistency of product quality. The selection and implementation of appropriate Design of Experiments (DoE) methodology to screen and optimize the formulation and process variables remain a major challenge. This review provides a comprehensive overview on QbD concepts in HME-based ASDs with an emphasis on DoE methodologies. Further, the information provided in this review can assist researchers in selecting a suitable design with optimal experimental conditions. Specifically, this review has focused on the prediction of drug-polymer miscibility, the elements and sequence of QbD, and various screening and optimization designs, to provide insights into the formulation and process variables that are encountered routinely in the production of HME-based ASDs.
      原文链接:
    • NSTL
    • Elsevier

    Mechanistic prediction of first-in-human dose for bispecific CD3/EpCAM T-cell engager antibody M701, using an integrated PK/PD modeling method

    Song, LingXue, JunshengZhang, JingLi, Si...
    10页
    查看更多>>摘要：Aim: M701 is a bispecific CD3/EpCAM T-cell engager antibody to treat malignant ascites. This study aimed to predict in vivo exposure-cytotoxicity relationship and human pharmacokinetics (PK) characteristics of M701, as well as to design optimal starting dose and effective dose for M701 first-in-human (FIH) study.
      原文链接:
    • NSTL
    • Elsevier

    Glaucoma: Management and Future Perspectives for Nanotechnology-Based Treatment Modalities

    El Hoffy, Nada M.Azim, Engy A. AbdelHathout, Rania M.Fouly, Marwa A....
    23页
    查看更多>>摘要：Glaucoma, being asymptomatic for relatively late stage, is recognized as a worldwide cause of irreversible vision loss. The eye is an impervious organ that exhibits natural anatomical and physiological barriers which renders the design of an efficient ocular delivery system a formidable task and challenge scientists to find alternative formulation approaches. In the field of glaucoma treatment, smart delivery systems for targeting have aroused interest in the topical ocular delivery field owing to its potentiality to oppress many treatment challenges associated with many of glaucoma types. The current momentum of nano-pharmaceuticals, in the development of advanced drug delivery systems, hold promises for much improved therapies for glaucoma to reduce its impact on vision loss.
      原文链接:
    • NSTL
    • Elsevier

    Ophthalmic delivery of hydrophilic drugs through drug-loaded oleogels

    Macoon, RussellChauhan, Anuj
    11页
    查看更多>>摘要：Purpose: Delivering ophthalmic drugs to the target tissues in eye is challenging due to transport barriers. Rapid tear clearance of the drug instilled as eye drops to treat anterior segment diseases results in a low ocular permeability of 1-5%. The blood-retina barrier and clearance mechanisms which eliminate drug from tears and ocular tissue make systemic or topical delivery techniques ineffective in delivering drugs to the back of the eye. Intravitreal injections into the eye are the only viable option even though repeated monthly injections increase risk for infections and retinal detachment. Controlled and sustained drug delivery could reduce the frequency of injections and lower the associated risk of side effects.
      原文链接:
    • NSTL
    • Elsevier