Abstract:
PURPOSE:Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their commercial development. To overcome these challenges a novel nanogel-based drug delivery system was designed. METHOD:The peptide novicidin was self-assembled with an octenyl succinic anhydride-modified analogue of hyaluronic acid, and this formulation was optimized using a microfluidics-based quality-by-design approach. RESULTS:By applying design-of-experiment it was demonstrated that the encapsulation efficiency of novicidin (15% to 71%) and the zeta potential (-24 to -57 mV) of the nanogels could be tailored by changing the preparation process parameters, with a maximum peptide loading of 36 ± 4%. The nanogels exhibited good colloidal stability under different ionic strength conditions and allowed complete release of the peptide over 14 days. Furthermore, self-assembly of novicidin with hyaluronic acid into nanogels significantly improved the safety profile at least five-fold and six-fold when tested in HUVECs and NIH 3T3 cells, respectively, whilst showing no loss of antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSION:Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Water JJ,Kim Y,Maltesen MJ,Franzyk H,Foged C,Nielsen HMdoi
10.1007/s11095-015-1658-6subject
Has Abstractpub_date
2015-08-01 00:00:00pages
2727-35issue
8eissn
0724-8741issn
1573-904Xjournal_volume
32pub_type
杂志文章abstract:PURPOSE:The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS:Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharm...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007657109012
更新日期:2000-12-01 00:00:00
abstract::Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is ap...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015888813741
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abstract:PURPOSE:Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. MET...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1887-3
更新日期:2016-06-01 00:00:00
abstract::Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015815614959
更新日期:1991-04-01 00:00:00
abstract:PURPOSE:To group microcrystalline celluloses (MCCs) using a combination of artificial neural network (ANN) and data clustering. METHODS:Radial basis function (RBF) network was used to model the torque measurements of the various MCCs. Output from the RBF network was used to group the MCCs using a data clustering techn...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-7690-6
更新日期:2004-12-01 00:00:00
abstract:PURPOSE:Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to improve the CNS exposure to (-)-carbovir ((-)-CBV). METHODS:Activation of (-)-6AC in vitro was assessed by incubations of rat brain tissue homogenates. The in vivo brain exposure to (-)-CBV was then examined in rats after iv infusions of either (-)-CBV (...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016229624703
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abstract::The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair fo...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/a:1015963128124
更新日期:1989-09-01 00:00:00
abstract:PURPOSE:To investigate differences in the cellular uptake and intracellular distribution of protein-bound doxorubicin in comparison to free doxorubicin and a liposomal formulation (CAELYX) METHODS: LXFL 529 lung carcinoma cells were incubated with an acid-sensitive transferrin and albumin conjugate of doxorubicin, a st...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011018525121
更新日期:2001-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was to obtain an in vitro/in vivo correlation for the sustained release of a protein from poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) microspheres. METHODS:Radiolabeled lysozyme was encapsulated in PEGT/PBT microspheres via a water-in-oil-in-water emu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/B:PHAM.0000019303.12086.d1
更新日期:2004-03-01 00:00:00
abstract:PURPOSE:Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway. Bupropion hydroxylation is catalyzed selectively by cytochrome P4502B6 (CYP2B6). CYP2B6-catalyzed bupropion hydroxylation has been used as an in vitro and in vivo phenotypic ...
journal_title:Pharmaceutical research
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doi:10.1007/s11095-008-9535-1
更新日期:2008-06-01 00:00:00
abstract::This study utilized different statistical techniques to evaluate the reliability (internal consistency) and the discriminant validity of the most widely used measures of organizational commitment and intention to quit (the employing organization). Data were obtained from a national mail survey of members of the Americ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018930718979
更新日期:1994-01-01 00:00:00
abstract::Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens or Pluronics can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Am...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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更新日期:2008-03-01 00:00:00
abstract:PURPOSE:To identify the aggregation mechanism and the stability characteristics of three different monoclonal antibodies under acidic conditions. METHODS:The aggregation kinetics is analyzed by a combination of light scattering, size exclusion chromatography and fluorescence techniques and the aggregation data are cor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0885-3
更新日期:2013-03-01 00:00:00
abstract::High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-rel...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018948924992
更新日期:1993-06-01 00:00:00
abstract:PURPOSE:To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides. METHODS:GR was administered...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016033124819
更新日期:1996-12-01 00:00:00
abstract:PURPOSE:The purpose of this study was to develop a new computational fluid dynamics (CFD)-based model of the complex transport and droplet drying kinetics within a laboratory-scale spray dryer, and relate CFD-predicted drying parameters to powder aerosolization metrics from a reference dry powder inhaler (DPI). METHOD...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02806-y
更新日期:2020-05-21 00:00:00
abstract:PURPOSE:The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetramethylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. METHODS:The study was carried out by investigati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016055517724
更新日期:1996-02-01 00:00:00
abstract:PURPOSE:To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells. METHODS:Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scan...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9760-7
更新日期:2009-03-01 00:00:00
abstract:PURPOSE:Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2570-2
更新日期:2019-02-22 00:00:00
abstract:PURPOSE:The structure-function relationship and mechanism of polycations as gene carriers have attracted considerable research interest in recent years. The present study was to investigate the relationship between polycation chain length and transfection efficiency (RCL-TE), and the corresponding mechanism by O-methyl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1211-4
更新日期:2014-04-01 00:00:00
abstract:PURPOSE:To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS:TNF-α inhibitors in their o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2341-x
更新日期:2018-02-05 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0739-z
更新日期:2012-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0425-6
更新日期:2011-08-01 00:00:00
abstract::The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018941810744
更新日期:1994-04-01 00:00:00
abstract:PURPOSE:Ruthenium complex is a potentially theranostic agent for cancer imaging and therapy, however its application is limited due to poor water-solubility and lack of tumor selectivity. To overcome the above drawbacks, pH-sensitive nanocapsule as a novel targeting carrier was designed to deliver ruthenium complex for...
journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2016-12-01 00:00:00
abstract:PURPOSE:To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice. METHODS:Target ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0963-6
更新日期:2013-05-01 00:00:00
abstract:PURPOSE:The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase. METHODS:Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0553-z
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020354809581
更新日期:2002-09-01 00:00:00
abstract::Human serum albumin (HSA) was encapsulated in a 50:50 copolymer of DL-lactide/glycolide in the form of microspheres. These microspheres were used as a model formulation to study the feasibility of controlling the release of large proteins over a 20- to 30-day period. We show that HSA can be successfully incorporated i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015948829632
更新日期:1990-11-01 00:00:00
abstract:PURPOSE:The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000048189.79606.6e
更新日期:2004-11-01 00:00:00