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Drug Delivery and Translational Research

Raffaella Sabatino, Serafina Battistelli, Mauro Magnani, Luigia Rossi
In tumor microenvironment, tumor-associated macrophages (TAMs) are implicated in cancer sustainment, metastasis, and drug resistance, raising a growing interest as targets in cancer therapy. Since the bisphosphonate zoledronate has proven to affect TAMs' functions, the anti-tumor effect of single or repeated administrations of red blood cells (RBCs) encapsulating zoledronate was evaluated in a mouse model of mammary carcinoma. The obtained results showed that loaded RBCs, but not free zoledronate, caused a significant (p < 0...
July 16, 2018: Drug Delivery and Translational Research
Mithila Boche, Varsha Pokharkar
Alendronate (ALD) is clinically indicated for the treatment of osteoporosis, but its therapeutic use has been marred by severe GIT adverse effects affecting quality of life in patients. In this study, we selected novel transdermal microemulsion (TDME) as a suitable carrier for ALD as the way of avoiding intestinal toxicity and highlighted its anti-osteoporotic efficacy with extensive pharmacokinetic and pharmacodynamic analysis. TDME achieved two fold increase in bioavailability as compared to oral administration in pharmacokinetic studies...
July 9, 2018: Drug Delivery and Translational Research
Mohammed Maniruzzaman, Ali Nokhodchi, Robert O Williams
No abstract text is available yet for this article.
July 5, 2018: Drug Delivery and Translational Research
Sumayah Al-Mahmood, Justin Sapiezynski, Olga B Garbuzenko, Tamara Minko
The major current conventional types of metastatic breast cancer (MBC) treatments include surgery, radiation, hormonal therapy, chemotherapy, or immunotherapy. Introducing biological drugs, targeted treatment and gene therapy can potentially reduce the mortality and improve the quality of life in patients with MBC. However, combination of several types of treatment is usually recommended. Triple negative breast cancer (TNBC) accounts for 10-20% of all cases of breast carcinoma and is characterized by the low expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2)...
July 5, 2018: Drug Delivery and Translational Research
Dalia H Abdelkader, Murtaza M Tambuwala, Christopher A Mitchell, Mohamed A Osman, Sanaa A El-Gizawy, Ahmed M Faheem, Mohamed El-Tanani, Paul A McCarron
Insulin plays an important role in the wound healing process, but its method of delivery to the wound bed and subsequent effect on rate of healing is less well investigated. In this study, we evaluated the therapeutic effectiveness of topical human insulin delivery using a nanoparticulate delivery system suspended in a structured hydrogel vehicle. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) of 202.6 nm diameter and loaded with 33.86 μg insulin per milligram of polymer were formulated using a modified double-emulsion solvent evaporation technique and dispersed in a dilatant hydrogel (poly(vinyl alcohol)-borate)...
July 3, 2018: Drug Delivery and Translational Research
Matthew J Herpin, Dominik Ebi, Noel T Clemens, Hugh D C Smyth
For the last several decades, the predominant method for delivering medicine to the surface of the eye has been the standard multiuse eye dropper. While being the most popular, this method has significant limitations. Recently, an effort has been made to explore the use of a directed toroidal vortex or "smoke ring" aerosol delivery system that may help overcome these limitations and enable delivery of precise amounts of formulation and drug to the ocular surface. Promising preliminary in vitro studies indicated dosing control, but the physical characteristics of the toriodal aerosol device performance and impaction forces related to patient comfort have yet to be established...
July 2, 2018: Drug Delivery and Translational Research
Riyadh B Al Asady, Mike J Hounslow, Agba D Salman
Understanding the compaction behaviour of the primary powder in the roller compaction process is necessary to be able to better control the quality of the product. In this study, the plastic deformation of the primary particles was evaluated by determining two mechanical properties: the nano-indentation hardness and the viscoelasticity of the primary powder. The nano-indentation hardness of eight different materials with a wide range of mechanical properties was determined by indenting the surface of the single primary particle, whereas the viscoelasticity was evaluated for a powder bed using the creep test...
June 26, 2018: Drug Delivery and Translational Research
Svenja Sladek, Clodagh Kearney, Daniel Crean, Pieter A J Brama, Lidia Tajber, Karolina Fawcett, Margot C Labberte, Bernadette Leggett, David J Brayden
Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study...
June 26, 2018: Drug Delivery and Translational Research
Sivakumar Vijayaraghavalu, Vinod Labhasetwar
Epigenetic modifications (e.g., DNA methylation or histone deacetylation) are commonly implicated in cancer chemoresistance. We previously showed that pretreating resistant MCF-7/ADR breast cancer cells with a demethylating agent (5-aza-2'-deoxycytidine (DAC)) or with an inhibitor of histone deacetylase (suberoylanilide hydroxamic acid (SAHA)) sensitized resistant cells to doxorubicin (DOX) treatment. However, even with increasing doses of DOX, a fraction of resistant cells remained nonresponsive to this pretreatment (~ 25% pretreated with DAC, ~ 45% with SAHA)...
June 26, 2018: Drug Delivery and Translational Research
Lucienne N Duru, Zhenzhen Quan, Talal Jamil Qazi, Hong Qing
Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration...
June 18, 2018: Drug Delivery and Translational Research
Hira Choudhury, Manisha Pandey, Pei Xin Chin, Yee Lin Phang, Jeng Yuen Cheah, Shu Chien Ooi, Kit-Kay Mak, Mallikarjuna Rao Pichika, Prashant Kesharwani, Zahid Hussain, Bapi Gorain
Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood-brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs)...
June 18, 2018: Drug Delivery and Translational Research
Song Li, Wei Li, Mark Prausnitz
Microneedle (MN) patches provide a simple method for delivery of drugs that might otherwise require hypodermic injection. Conventional MN patch fabrication methods typically can load only one or possibly multiple miscible agents with the same formulation on all MNs, which limits the combination and spatial distribution of drugs and formulations having different properties (such as solubility) in a single patch. In this study, we coated MNs individually instead of coating all MNs from the same formulation, making possible a patch where each individual MN is coated with different formulations and drugs...
June 12, 2018: Drug Delivery and Translational Research
Kiran P Sawant, Ritesh Fule, Mohammed Maniruzzaman, Purnima D Amin
The current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology. Either Eudragit®S100 and Eudragit®L100 alone or in combination with release modifying agent Polyox™ WSR 303 and Eudragit®L100-55 were processed to obtain complete and faster release. Metoprolol succinate with similar solubility parameters to polymer was dispersed in polymer matrix and was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM)...
June 12, 2018: Drug Delivery and Translational Research
Cheng Loong Ngan, Azren Aida Asmawi
Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity...
June 7, 2018: Drug Delivery and Translational Research
Rita Haj-Ahmad, Manoochehr Rasekh, Kazem Nazari, Ekhoerose V Onaiwu, Bushra Yousef, Stuart Morgan, David Evans, Ming-Wei Chang, John Hall, Chris Samwell, Zeeshan Ahmad
Electrohydrodynamic atomization (EHDA) is an emerging technique for the production of micron and nano-scaled particles. The process often involves Taylor cone enablement, which results in a fine spray yielding formulated droplets, which then undergo drying during deposition. In this work, novel multi-tip emitter (MTE) devices were designed, engineered and utilized for potential up-scaled EHDA, by comparison with a conventional single-needle system. To demonstrate this, the active ketoprofen (KETO) was formulated using polyvinylpyrrolidone (PVP) polymer as the matrix material...
June 5, 2018: Drug Delivery and Translational Research
Sebastiano La Maestra, Guido Frosina, Rosanna T Micale, Chiara D'Oria, Silvano Garibaldi, Antonio Daga, Alessandra Pulliero, Alberto Izzotti
Oligonucleotide overloading results in type I interferonopathies such as the Aicardi-Goutiéres Syndrome, a progressive encephalopathy determined by an immune response against endogenous DNA/RNA molecules. No therapy targeting pathogenic mechanisms is available for affected patients. Accordingly, we set up an in vitro/in vivo experimental model aimed at reproducing the pathogenic mechanisms of type I interferonopathies, in order to develop an effective pharmacological modulation and toxicological alterations caused by intracranial delivery of encapsulated CpG...
June 4, 2018: Drug Delivery and Translational Research
Forouhe Zahir-Jouzdani, Masoud Soleimani, Mirgholamreza Mahbod, Fatemeh Mottaghitalab, Faezeh Vakhshite, Ehsan Arefian, Saeed Shahhoseini, Rasoul Dinarvand, Fatemeh Atyabi
Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFβ1 ) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti-fibrotic TGF-β1 siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-β1 siRNA loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-β 1 and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts...
June 4, 2018: Drug Delivery and Translational Research
Phillip Dixon, Tanushri Ghosh, Kalyani Mondal, Aditya Konar, Anuj Chauhan, Sarbani Hazra
Chemical injury by alkali burn is a major cause of corneal blindness in the clinical setting. Current management advocates multiple therapies aimed to prevent inflammation, initiate quick re-epithelialization, arrest the fibrosis, and avoid dry eye and pain by using bandage contact lenses. We hypothesized sustained delivery of the anti-inflammatory, antifibrotic drug pirfenidone through vitamin E-loaded contact lenses as a logical single approach to counter the pathology involved. Vitamin E particles were created in situ in commercial silicon hydrogel contact lenses by soaking the lenses in a vitamin E-ethanol solution...
June 1, 2018: Drug Delivery and Translational Research
Ting-Ting Liu, Kai Chen, Qiao Wang
Micro-needles and sonophoresis are two physical methods for enhancing skin permeation for transdermal drug delivery. A solid micro-needle system with vertical vibration was integrated and its effects on transdermal drug delivery were studied. Evan's blue (EB) staining and histological evaluation were performed to reveal the skin morphology and micro-conduits created by vibrating micro-needles. Trans-epidermal water loss (TEWL) and infection studies on rat's skin after vibrating micro-needle treatment were performed to evaluate the safety of the treatment...
June 1, 2018: Drug Delivery and Translational Research
Ankit Parikh, Krishna Kathawala, Yunmei Song, Xin-Fu Zhou, Sanjay Garg
Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy...
May 29, 2018: Drug Delivery and Translational Research
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