Abstract:
OBJECTIVE:The objective of this work was to determine plasma protein adsorption and macrophage phagocytosis of biodegradable polyanhydride, polylactic acid and polylactic-co-glycolic acid microspheres prepared by both spray-drying and solvent evaporation techniques. METHODS:Microspheres were characterized by scanning electron microscopy (SEM), confocal laser microscopy, particle size distribution and zeta (zeta) potential determination. Plasma protein adsorption onto the microspheres was determined using a fluoroaldehyde reagent. Phagocytosis was evaluated by incubating microspheres containing the angiotensin II antagonist, L-158,809, with the macrophages in the presence or absence of the phagocytosis inhibitor cythochalasin D. The extent of phagocytosis was established by fluorescence determination of L-158,809 and by optical microscopy. The effect of amphiphilic poly(ethylene glycol) (PEG) derivatives on phagocytosis was determined using PEG-distearate incorporated into the microspheres. RESULTS:The average diameter of the microspheres, which depended on the polymer and the initial formulation, ranged from 0.9 to 3.2 micrometers. Zeta potential studies showed strong negative values irrespective of the polymer used for the spray-dried formulations. The zeta potential was masked by the incorporation of PEG 400- or PEG 1,400-distearate in the formulation. Confocal laser microscopy showed a homogenous dispersion of PEG (measured as PEG-fluorescein) in the microspheres. Protein adsorption was not observed for any of the microsphere formulations following incubation with bovine serum. Incubation of microspheres with murine macrophages showed that PEG-distearate inhibited phagocytosis at appropriate levels (0.1% w/w). Higher levels > 1% w/w of PEG-distearate) resulted in enhanced association with macrophages, despite the presence of the phagocytosis inhibitor cytochalasin D, indicating fusion between the microspheres and the plasma membrane. CONCLUSIONS:These results demonstrate that spray-dried PEG-containing microspheres can be manufactured and that an appropriate concentration of this excipient in microspheres results in decreased phagocytosis.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Lacasse FX,Filion MC,Phillips NC,Escher E,McMullen JN,Hildgen Pdoi
10.1023/a:1011935222652subject
Has Abstractpub_date
1998-02-01 00:00:00pages
312-7issue
2eissn
0724-8741issn
1573-904Xjournal_volume
15pub_type
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9301-9
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018993610801
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015841715384
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011973625803
更新日期:1998-04-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2011-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1026147620304
更新日期:2003-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018901912619
更新日期:1994-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018986827350
更新日期:1993-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011994230346
更新日期:1998-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9365-6
更新日期:2008-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11095-015-1667-5
更新日期:2015-09-01 00:00:00
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journal_title:Pharmaceutical research
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doi:10.1007/s11095-010-0277-5
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journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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更新日期:2014-06-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016356926714
更新日期:1984-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015984300692
更新日期:1988-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1658-6
更新日期:2015-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023831102203
更新日期:2003-06-01 00:00:00
abstract::Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secon...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015973425708
更新日期:1988-08-01 00:00:00
abstract:PURPOSE:To examine the effect of particle size and morphology on aerosol dispersion using jet-milled and spray-dried mannitol particles in narrow size distributions within the respirable range. METHODS:Particle size and morphology were examined by laser diffraction and scanning electron microscopy, respectively. Aeros...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000033007.27278.60
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016028707130
更新日期:1996-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0823-4
更新日期:2012-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2209-0
更新日期:2017-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-0037-6
更新日期:2010-04-01 00:00:00
abstract::Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fib...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-014-1497-x
更新日期:2015-02-01 00:00:00