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Drug Delivery and Translational Research

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https://www.readbyqxmd.com/read/28070705/enzymatic-activation-of-double-targeted-5-o-l-valyl-decitabine-prodrug-by-biphenyl-hydrolase-like-protein-and-its-molecular-design-basis
#1
Wenhui Tao, Dongyang Zhao, Mengchi Sun, Meng Li, Xiangyu Zhang, Zhonggui He, Yinghua Sun, Jin Sun
A primary focus of this research was to explore the activation process and mechanism of decitabine (5-aza-2'-deoxycytidine, DAC) prodrug. Recently, it has been reported that biphenyl hydrolase-like protein (BPHL) can play an important role in the activation of some amino acid nucleoside prodrugs with a general preference for hydrophobic amino acids and 5'-esters. Therefore, we put forward a bold hypothesis that this novel enzyme may be primarily responsible for the activation process of DAC prodrug as well...
January 9, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28050893/novel-route-of-insulin-delivery-using-an-implant-mediated-drug-delivery-system
#2
Young-Seok Park
Patients with diabetes mellitus (DM) frequently require multiple painful injections of insulin to manage their blood glucose level. A newly introduced, modified titanium implant, the implant-mediated drug delivery system (IMDDS), has the advantage of sustained, needle-free drug delivery. We evaluated the feasibility of the IMDDS as an alternative route of insulin delivery in an alloxan-induced rabbit DM model. Among a total of 30 rabbits with IMDDSs, 25 survived the induction and had a blood glucose level (BGL) higher than 300 mg/dl...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28050892/in-vivo-pharmacological-evaluation-and-efficacy-study-of-methotrexate-encapsulated-polymer-coated-layered-double-hydroxide-nanoparticles-for-possible-application-in-the-treatment-of-osteosarcoma
#3
Sayantan Ray, Suman Saha, Biswanath Sa, Jui Chakraborty
Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28050891/a-novel-mechanism-governing-the-transcriptional-regulation-of-abc-transporters-in-mdr-cancer-cells
#4
Jamie F Lu, Deep Pokharel, Mary Bebawy
P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1) are the main drug efflux transporters associated with treatment failure in cancer. Much attention has been focused on the molecular mechanisms regulating the expression of these transporters as a viable approach for identifying novel drug targets in circumventing cancer multidrug resistance (MDR) clinically. In this paper, we examine the role of miR-326 in the context of its intercellular transfer between cancer cells by extracellular membrane vesicles called microparticles (MPs)...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28050890/nanoengineered-strategies-for-sirna-delivery-from-target-assessment-to-cancer-therapeutic-efficacy
#5
REVIEW
Dinesh Kumar Mishra, Neelam Balekar, Pradyumna Kumar Mishra
The promise of RNA interference (RNAi) technology in cancer therapeutics aims to deliver small interfering RNA (siRNA) for silencing of gene expression in cell type-specific pathway. However, the challenge for the delivery of stable siRNA is hindered by an immune-hostile tumor microenvironment and physiological barriers of the circulatory system. Therefore, the development and validation of safe, stable, and efficient nanoengineered delivery systems are highly essential for effective delivery of siRNA into cancer cells...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27981502/skin-targeting-of-resveratrol-utilizing-solid-lipid-nanoparticle-engrossed-gel-for-chemically-induced-irritant-contact-dermatitis
#6
S N Shrotriya, N S Ranpise, B V Vidhate
Irritant contact dermatitis (ICD) is a chronic and relapsing skin disease with severe eczematous lesions. Despite its growing prevalence, therapeutic treatments remain limited. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation, and increase in transepidermal water loss. An innovative dermal treatment is essential to reduce the side effects of corticosteroids. Topical resveratrol (RES), although effective for ICD, is a challenging molecule due to low solubility and poor bioavailability...
December 15, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27928713/corticosteroid-transdermal-delivery-significantly-improves-arthritis-pain-and-functional-disability
#7
Tommaso Iannitti, Michael F McDermott, Carmen Laurino, Andrea Malagoli, Beniamino Palmieri
Arthritis is characterized by pain and functional limitation affecting the patients' quality of life. We performed a clinical study to investigate the efficacy of a betamethasone valerate medicated plaster (Betesil) in improving pain and functional disability in patients with arthritis and osteoarthritis. We enrolled 104 patients affected by osteoarthritis (n = 40) or arthritis (n = 64) in different joints. Patients received diclofenac sodium cream (2 g, four times a day) or a 2.25-mg dose of Betesil applied to the painful joint every night before bedtime for 10 days...
December 7, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27924469/a-methylcellulose-and-collagen-based-temperature-responsive-hydrogel-promotes-encapsulated-stem-cell-viability-and-proliferation-in-vitro
#8
Christina Payne, Eimear B Dolan, Janice O'Sullivan, Sally-Ann Cryan, Helena M Kelly
With the number of stem cell-based therapies emerging on the increase, the need for novel and efficient delivery technologies to enable therapies to remain in damaged tissue and exert their therapeutic benefit for extended periods, has become a key requirement for their translation. Hydrogels, and in particular, thermoresponsive hydrogels, have the potential to act as such delivery systems. Thermoresponsive hydrogels, which are polymer solutions that transform into a gel upon a temperature increase, have a number of applications in the biomedical field due to their tendency to maintain a liquid state at room temperature, thereby enabling minimally invasive administration and a subsequent ability to form a robust gel upon heating to physiological temperature...
December 6, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27924468/whether-a-novel-drug-delivery-system-can-overcome-the-problem-of-biofilms-in-respiratory-diseases
#9
REVIEW
Kamal Dua, Shakti D Shukla, Rakesh K Tekade, Philip M Hansbro
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches...
December 6, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27896668/target-specific-delivery-of-sirna-into-hepatoma-cells-cytoplasm-by-bifunctional-carrier-peptide
#10
Xiaoxuan Liu, Lin Zhu, Jingjing Ma, Xinxiao Qiao, Dunwan Zhu, Lanxia Liu, Xigang Leng
RNA interference (RNAi) is among the most potential approach for the therapy of hepatocellular carcinoma and the major barrier hindering siRNA therapeutics is the low efficiency of delivery to the desired cells. The current study aimed at developing a novel peptide for more efficient hepatoma targeted siRNA delivery, by combining luteinizing hormone-releasing hormone with hepatoma targeting specificity and MPG(△NLS) with cytoplasm-delivery tendency. The developed bifunctional peptide LHRH-MPG(△NLS) and siRNA were mixed together and resulted in LHRH-MPG(△NLS)/siRNA polyplexes through self-assembly...
November 28, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27873080/evaluation-of-the-drug-solubility-and-rush-ageing-on-drug-release-performance-of-various-model-drugs-from-the-modified-release-polyethylene-oxide-matrix-tablets
#11
Saeed Shojaee, Ali Nokhodchi, Mohammed Maniruzzaman
Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide...
November 21, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27864786/clinical-pharmacokinetics-of-an-amorphous-solid-dispersion-tablet-of-elacridar
#12
Emilia Sawicki, Remy B Verheijen, Alwin D R Huitema, Olaf van Tellingen, Jan H M Schellens, Bastiaan Nuijen, Jos H Beijnen, Neeltje Steeghs
Elacridar is an inhibitor of the permeability glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) and is a promising absorption enhancer of drugs that are substrates of these drug-efflux transporters. However, elacridar is practically insoluble in water, resulting in low bioavailability which currently limits its clinical application. We evaluated the in vitro dissolution and clinical pharmacokinetics of a novel amorphous solid dispersion (ASD) tablet containing elacridar. The dissolution from ASD tablets was compared to that from a crystalline powder mixture in a USP type II dissolution apparatus...
November 18, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27848224/micrornas-as-therapeutics-for-future-drug-delivery-systems-in-treatment-of-lung-diseases
#13
REVIEW
Kamal Dua, Nicole G Hansbro, Paul S Foster, Philip M Hansbro
The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system...
November 15, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27848223/the-third-annual-brds-on-research-and-development-of-nucleic-acid-based-nanomedicines
#14
Amit Kumar Chaudhary, Ram I Mahato
The completion of human genome project, decrease in the sequencing cost, and correlation of genome sequencing data with specific diseases led to the exponential rise in the nucleic acid-based therapeutic approaches. In the third annual Biopharmaceutical Research and Development Symposium (BRDS) held at the Center for Drug Discovery and Lozier Center for Pharmacy Sciences and Education at the University of Nebraska Medical Center (UNMC), we highlighted the remarkable features of the nucleic acid-based nanomedicines, their significance, NIH funding opportunities on nanomedicines and gene therapy research, challenges and opportunities in the clinical translation of nucleic acids into therapeutics, and the role of intellectual property (IP) in drug discovery and development...
November 15, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27815776/microwaved-bacterial-cellulose-based-hydrogel-microparticles-for-the-healing-of-partial-thickness-burn-wounds
#15
Manisha Pandey, Najwa Mohamad, Wan-Li Low, Claire Martin, Mohd Cairul Iqbal Mohd Amin
Burn wound management is a complex process because the damage may extend as far as the dermis which has an acknowledged slow rate of regeneration. This study investigates the feasibility of using hydrogel microparticles composed of bacterial cellulose and polyacrylamide as a dressing material for coverage of partial-thickness burn wounds. The microparticulate carrier structure and surface morphology were investigated by Fourier transform infrared, X-ray diffraction, elemental analysis, and scanning electron microscopy...
November 4, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27812915/development-of-self-nanoemulsifying-drug-delivery-system-for-oral-bioavailability-enhancement-of-valsartan-in-beagle-dogs
#16
Zhenbao Li, Wenjuan Zhang, Yan Gao, Rongwu Xiang, Yan Liu, Mingming Hu, Mei Zhou, Xiaohong Liu, Yongjun Wang, Zhonggui He, Yinghua Sun, Jin Sun
Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology...
November 3, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27807769/nanogels-of-methylcellulose-hydrophobized-with-n-tert-butylacrylamide-for-ocular-drug-delivery
#17
Marion Jamard, Todd Hoare, Heather Sheardown
While eye drops account for the majority of ophthalmic formulation for drug delivery, their efficiency is limited by rapid pre-corneal loss. In this study, we investigate nanogel suspensions in order to improve the topical ocular therapy by reducing dosage and frequency of administration. We synthesized self-assembling nanogels of 140 nm by grafting side chains of poly(N-tert-butylacrylamide) (PNtBAm) on methylcellulose via cerium ammonium nitrate. Successful grafting of PNtBAm onto methylcellulose (MC) was confirmed by both NMR and ATR...
November 2, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27798766/a-comprehensive-insight-on-ocular-pharmacokinetics
#18
REVIEW
Vibhuti Agrahari, Abhirup Mandal, Vivek Agrahari, Hoang M Trinh, Mary Joseph, Animikh Ray, Hicheme Hadji, Ranjana Mitra, Dhananjay Pal, Ashim K Mitra
The eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment models of ocular drug delivery have been developed for describing the absorption, distribution, and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems, and routes of administration is discussed including factors affecting intraocular bioavailability...
October 31, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27766599/fatty-acid-microemulsion-for-the-treatment-of-neonatal-conjunctivitis-quantification-characterisation-and-evaluation-of-antimicrobial-activity
#19
Ummara Butt, Amr ElShaer, Lori A S Snyder, Athina Chaidemenou, Raid G Alany
Fatty acids (FAs) are used by many organisms as defence mechanism against virulent bacteria. The high safety profile and broad spectrum of activity make them potential alternatives to currently used topical antibiotics for the treatment of eye infections in neonates. The current study utilised a Design of Experiment approach to optimise the quantification of five fatty acids namely; lauric acid, tridecanoic acid, myristoleic acid, palmitoleic acid and α-linolenic acid. The significance of the influence of the experimental parameters such as volume of catalyst, volume of n-hexane, incubation temperature, incubation time and the number of extraction steps on derivatisation was established by statistical screening with a factorial approach...
December 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27709355/rapidly-dissolving-polymeric-microneedles-for-minimally-invasive-intraocular-drug-delivery
#20
Raghu Raj Singh Thakur, Ismaiel A Tekko, Farhan Al-Shammari, Ahlam A Ali, Helen McCarthy, Ryan F Donnelly
In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate-dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation...
December 2016: Drug Delivery and Translational Research
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