Abstract：
PURPOSE:Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral injectables that deliver drug for months at a time have moved into late phase clinical trials. Unfortunately, these solid phase crystal formulations have inherent drawbacks in potential dose dumping and a greater likelihood for burst release of drug compared to polymeric formulations. METHODS:Using electrospinning, acetalated dextran scaffolds containing the protease inhibitor saquinavir were created. Grinding techniques were then used to process these scaffolds into injectables which are termed saquinavir microconfetti. Microconfetti was analyzed for in vitro and in vivo release kinetics. RESULTS:Highly saquinavir loaded acetalated dextran electrospun fibers were able to be formed and processed into saquinavir microconfetti while other polymers such as poly lactic-co-glycolic acid and polycaprolactone were unable to do so. Saquinavir microconfetti release kinetics were able to be tuned via drug loading and polymer degradation rates. In vivo, a single subcutaneous injection of saquinavir microconfetti released drug for greater than a week with large tissue retention. CONCLUSIONS:Microconfetti is a uniquely tunable long acting injectable that would reduce the formation of adherence related HIV resistance. Our findings suggest that the injectable microconfetti delivery system could be used for long acting controlled release of saquinavir and other hydrophobic small molecule drugs.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Collier MA,Gallovic MD,Bachelder EM,Sykes CD,Kashuba A,Ainslie KMdoi
10.1007/s11095-016-1936-ysubject
Has Abstractpub_date
2016-08-01 00:00:00pages
1998-2009issue
8eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-016-1936-yjournal_volume
33pub_type
杂志文章abstract：PURPOSE:Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects. METHODS:To study...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000048199.94510.b0
更新日期：2004-11-01 00:00:00
abstract：PURPOSE:The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. METHOD:Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1335-1
更新日期：2014-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016405126656
更新日期：1996-11-01 00:00:00
abstract：PURPOSE:To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS:The ASES technique using high pressure carbon dioxide modified with e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000008053.69903.c1
更新日期：2003-12-01 00:00:00
abstract：PURPOSE:The present investigation describes a formulative study for the development of innovative drug delivery systems for bromocriptine. METHODS:Solid lipid nanoparticles (SLN) based on different lipidic components have been produced and characterized. Morphology and dimensional distribution have been investigated b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9514-y
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013002414678
更新日期：2001-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2307-z
更新日期：2018-01-05 00:00:00
abstract：PURPOSE:The in vitro inhibitory effect of Docetaxel (DTX) and Everolimus (EVR) alone and together in poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) nanocarriers on angiogenic processes and acute toxicity in mice was evaluated. METHODS:PEG-b-PLA DTX and/or EVR nanocarriers were characterized for size, dr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1188-z
更新日期：2014-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015956104500
更新日期：1989-06-01 00:00:00
abstract：:The topical antifungal Sch-39304 is a racemic compound comprised of two enantiomers, Sch-42427 and Sch-42426, only one of which (Sch-42427) is pharmacologically active. The pure enantiomers have a lower melting point and, therefore, a higher solubility than the racemic compound. Because of these differences in physico...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018945618264
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. METHODS:An indomethacin hydrolyzing enzyme was purified to homoge...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016061614399
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1324-4
更新日期：2014-09-01 00:00:00
abstract：:Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018916811904
更新日期：1993-01-01 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
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5280-x
更新日期：2005-08-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9066-6
更新日期：2006-09-01 00:00:00
abstract：:We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+aH+ + ko + kHO-aHO- and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015809408908
更新日期：1991-11-01 00:00:00
abstract：:The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent wi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015834114359
更新日期：1991-12-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0944-9
更新日期：2013-04-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-007-9369-2
更新日期：2007-11-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018932705370
更新日期：1993-08-01 00:00:00
abstract：PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9170-7
更新日期：2007-03-01 00:00:00
abstract：:An alternative procedure for the simultaneous determination of trimethoprim and sulfamethoxazole in an intravenous pharmaceutical formulation is presented. Infrared spectra of 14 calibration and 6 validation samples were collected using Fourier transform-infrared/attenuated total reflectance (FT-IR/ATR). Partial least...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015957632242
更新日期：1989-07-01 00:00:00
abstract：PURPOSE:This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS:In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1873-9
更新日期：2016-06-01 00:00:00
abstract：:The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vei...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016374508542
更新日期：1984-01-01 00:00:00
abstract：:The application of supercritical fluid (SF) processing in pharmaceutical research is increasing particularly in the field of particle formation for drug delivery systems. The SF processes have benefits over the existing particle formation methods in terms of improved control, flexibility and operational ease. This rev...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：1999-07-01 00:00:00
abstract：PURPOSE:Monoamine oxidases (MAOs) are non-CYP enzymes that contribute to systemic elimination of therapeutic agents, and localized on mitochondrial membranes. The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). METHODS:...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2140-4
更新日期：2017-06-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetics of simvastatin (SV) and simvastatin acid (SVA), a lactone-acid pair known to undergo reversible metabolism, and to better understand mechanisms underlying pharmacokinetic interactions observed between SV and gemfibrozil. METHODS:Pharmacokinetic studies were conducted after ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6037-2
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. METHODS:Spray dried mannitol (SDM) partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1132-2
更新日期：2014-01-01 00:00:00
abstract：PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0830-5
更新日期：2012-12-01 00:00:00
