Abstract：
PURPOSE:This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic "nano-shields" and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactions. METHODS:Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared with a hydrophilic PEGylated "nano-shield" inserted at different levels by hydrophobic anchoring using either a phospholipid-PEG conjugate or the copolymer PLGA-block-PEG by an emulsification/diffusion method. Surface and bulk analysis was performed including X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) and zeta potential. Cellular uptake was investigated in RAW 264.7 macrophages by flow cytometry. RESULTS:Sub-micron nanoparticles were formed and the combination of (NMR) and XPS revealed increasing PEG levels at the particle surface at higher PLGA-b-PEG copolymer levels. Reduced cellular interaction with RAW 264.7 cells was demonstrated that correlated with greater surface presentation of PEG. CONCLUSION:This work demonstrates a versatile procedure for decorating nanoparticle surfaces with hydrophilic "nano-shields". XPS in combination with NMR enabled precise determination of PEG at the outmost surface to predict and optimize the biological performance of nanoparticle-based drug delivery.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Ebbesen MF,Whitehead B,Ballarin-Gonzalez B,Kingshott P,Howard KAdoi
10.1007/s11095-013-1018-3subject
Has Abstractpub_date
2013-07-01 00:00:00pages
1758-67issue
7eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract：PURPOSE:To describe the pharmacokinetics of SK&F 107647, a synthetic hematoregulatory peptide, in healthy volunteers and in patients with adenocarcinoma. METHODS:SK&F 107647 pharmacokinetics were evaluated in 2 dose-escalation studies. Volunteers received SK&F 107647 as single 15-minute iv infusion doses of 1, 10, 100...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007512617139
更新日期：2000-04-01 00:00:00
abstract：PURPOSE:The purpose of this human intestinal perfusion study was to investigate the transport and metabolism of R/S-verapamil in the human jejunum (in vivo). METHODS:A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011916329863
更新日期：1998-06-01 00:00:00
abstract：PURPOSE:To determine the factors influencing "solid solubility" and phase separation kinetics of drugs from amorphous solid dispersions. METHODS:Solid dispersions of griseofulvin-poly(vinyl pyrrolidone) (PVP) and indoprofen-PVP were prepared using solvent evaporation technique. Dispersions demonstrating single Tg were...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-1882-y
更新日期：2005-03-01 00:00:00
abstract：PURPOSE:The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS:Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately follo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9175-7
更新日期：2006-02-01 00:00:00
abstract：:Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015872617511
更新日期：1990-02-01 00:00:00
abstract：PURPOSE:Percutaneous absorption assays of molecules for pharmaceutical and cosmetology purposes are important to determine the bioavailability of new compounds, once topically applied. The current method of choice is to measure the rate of diffusion through excised human skin using a diffusion cell. This method however...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1654-x
更新日期：2015-08-01 00:00:00
abstract：:We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016363316777
更新日期：1985-05-01 00:00:00
abstract：:The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. beta-Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018974131236
更新日期：1993-12-01 00:00:00
abstract：PURPOSE:The purpose of this study was to stabilize the vinca alkaloids, vincristine sulfate (VCR) and vinblastine sulfate (VBL), in poly(lactide-co-glycolide) (PLGA) microspheres and to release the drugs in a sustained manner for more than a month. METHODS:An oil-in-oil emulsion-solvent extraction method was used to e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007522013835
更新日期：2000-06-01 00:00:00
abstract：PURPOSE:To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS:We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeabil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018887216098
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4-10 fusion protein (IL4-10 FP) on in vitro and in vivo bioactivity and evaluated the effect of differential sialylation on pharmacokinetic param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2744-y
更新日期：2019-12-26 00:00:00
abstract：:The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tend...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016292232513
更新日期：1995-03-01 00:00:00
abstract：PURPOSE:To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. METHODS:Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissoluti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0695-7
更新日期：2012-10-01 00:00:00
abstract：PURPOSE:Following extracellular drug clearance, we analyzed the rate of doxorubicin efflux from the nucleus of three human leukemic cells (K562, Molt4 and CCRF-CEM) and related it to their differential sensitivity to this drug, after a short drug pulse. RESULTS:For many pulse-chase regimes, K562 cell viability was lea...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9369-2
更新日期：2007-11-01 00:00:00
abstract：:Antibody drug conjugates (ADCs) are a class of therapeutics that combine the target specificity of an antibody with the potency of a chemotherapeutic. This therapeutic strategy can significantly expand the therapeutic index of a chemotherapeutic by minimizing the systemic exposure and associated toxicity of the chemot...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-012-0800-y
更新日期：2012-09-01 00:00:00
abstract：PURPOSE:Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9834-1
更新日期：2009-05-01 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：:This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015841715384
更新日期：1991-06-01 00:00:00
abstract：:The effect of buprenorphine on bremazocine-induced diuresis was tested in the rat to determine the nature of buprenorphine's action at the ϰ opioid receptor. Both morphine-tolerant and naive rats were used to account for possible antidiuretic effects of buprenorphine at the µ site. Separate experiments established tha...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016340106299
更新日期：1985-07-01 00:00:00
abstract：PURPOSE:We recently developed prostaglandin E(1) (PGE(1))-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed wi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9943-x
更新日期：2009-10-01 00:00:00
abstract：:Animal models are used commonly in various stages of drug discovery and development to aid in the prospective assessment of drug-drug interaction (DDI) potential and the understanding of the underlying mechanism for DDI of a drug candidate. In vivo assessments in an appropriate animal model can be very valuable, when ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-010-0157-z
更新日期：2010-09-01 00:00:00
abstract：:Molecular modeling has been used to study the complexation between alpha, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. The computer program SYBYL 5.3 and the Tripos force field (version 5.2) were used for all the calculations. Three-dimensional structures of ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015816215751
更新日期：1991-10-01 00:00:00
abstract：PURPOSE:Topoisomerase II (Topo II) preferentially cuts DNA at alternating purine-pyrimidine repeats. Different Topo II poisons may affect Topo II to produce distinct drug-specific DNA cleavage patterns. GL331 is a new podophyllotoxin derivative exhibiting potent Topo II-poisoning activity. Therefore, the sequence selec...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011048831698
更新日期：2001-06-01 00:00:00
abstract：PURPOSE:The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS:The erodible plugs were either prepared by direct compression followed by placing the tablets in...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011940718534
更新日期：1998-03-01 00:00:00
abstract：PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014430631844
更新日期：2002-03-01 00:00:00
abstract：PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of pacli...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-4581-4
更新日期：2005-06-01 00:00:00
abstract：:The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016312827680
更新日期：1985-09-01 00:00:00
abstract：PURPOSE:The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. METHODS:A hydrophilic model molecule, inulin, was encapsulated within positively charged and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-4591-2
更新日期：2005-06-01 00:00:00
abstract：PURPOSE:To engineer optimized near-infrared (NIR) active thermosensitive liposomes to potentially achieve image-guided delivery of chemotherapeutic agents. METHODS:Thermosensitive liposomes were surface-coated with either polyethylene glycol or dextran. Differential scanning calorimetry and calcein release studies wer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0738-0
更新日期：2012-08-01 00:00:00
