Abstract：
PURPOSE:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to microinfuse sulforhodamine solution at constant pressure. Flow rate was determined as a function of experimental parameters, such as microneedle insertion and retraction distance, infusion pressure, microneedle tip geometry, presence of hyaluronidase, and time. RESULTS:Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15-96 microl/h. Partial retraction of microneedles increased flow rate up to 11.6-fold. Infusion flow rate was also increased by greater insertion depth, larger infusion pressure, use of a beveled microneedle tip, and the presence of hyaluronidase such that flow rates ranging from 21 to 1130 microl/h were achieved. These effects can be explained by removing or overcoming the large flow resistance imposed by dense dermal tissue, compressed during microneedle insertion, which blocks flow from the needle tip. CONCLUSIONS:By partially retracting microneedles after insertion and other methods to overcome flow resistance of dense dermal tissue, protocols can be designed for hollow microneedles to microinfuse fluid at therapeutically relevant rates.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Martanto W,Moore JS,Kashlan O,Kamath R,Wang PM,O'Neal JM,Prausnitz MRdoi
10.1007/s11095-005-8498-8subject
Has Abstractpub_date
2006-01-01 00:00:00pages
104-13issue
1eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract：PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011902625609
更新日期：1999-04-01 00:00:00
abstract：PURPOSE:To investigate the properties of phenylboronic acid-functional poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their compatibility with COS-7 cells. METHODS:Copolymers of phenylboronic acid-functional poly(amid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1688-0
更新日期：2015-09-01 00:00:00
abstract：PURPOSE:To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide. METHODS:The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Cir...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1298-2
更新日期：2014-08-01 00:00:00
abstract：:A new technique has been developed to calculate rapidly the solid-state room-temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015865319250
更新日期：1992-07-01 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 identify the molecules responsible for amyloid beta-peptide (1-40) (Abeta(1-40)) uptake by the liver, which play a major role in the systemic clearance of Abeta(1-40). METHODS:The liver uptake index method was used to examine the mechanisms of Abeta(1-40) uptake by the liver in vivo. RESULTS:[125I]Abeta(1-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0208-7
更新日期：2006-07-01 00:00:00
abstract：PURPOSE:A pattern fitting procedure using X-ray powder diffraction patterns was applied to study the crystallization kinetics of amorphous griseofulvin. From the optimized parameters obtained by pattern fitting, a change in the quantity and quality of griseofulvin crystals with crystallization was also investigated. M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9204-1
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:Within-subject dependency of observations has a strong impact on the evaluation of population pharmacokinetic (PK) and/or pharmacodynamic (PD) models. To our knowledge, none of the current model evaluation tools correctly address this issue. We present a new method with a global test and easy diagnostic plot wh...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0422-9
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1021457911533
更新日期：2002-12-01 00:00:00
abstract：PURPOSE:To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX). METHOD:Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs),...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1251-9
更新日期：2014-05-01 00:00:00
abstract：PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016071311190
更新日期：1996-10-01 00:00:00
abstract：PURPOSE:There is evidence that cholesterol affects the ATPase and transport functions of P-glycoprotein (P-gp). To study the influence of cholesterol on P-gp in a well defined lipid environment, we reconstituted P-gp in egg phosphatidylcholine (PhC) and PhC/cholesterol proteoliposomes with negligible residual amounts o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9326-0
更新日期：2007-11-01 00:00:00
abstract：:A procedure is described that is suitable for the radioimmunoassay (RIA) of 9-[(l,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) in plasma or serum at concentrations as low as 0.7 ng/ml (2.75 × 10(-9) M). Antiserum was prepared by coupling DHPG monohemisuccinate to bovine serum albumin and immunizing rabbits with the re...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016397520991
更新日期：1986-04-01 00:00:00
abstract：PURPOSE:The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even tho...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2300-6
更新日期：2018-02-21 00:00:00
abstract：:We describe a simplified and rapid liquid chromatographic determination of antipyrine clearance (CLAP) calculated from peak height ratios of drug/internal standard. Saliva or plasma was collected 24 hr after the oral administration of 1 g of antipyrine to the subject. A 25-microliter aliquot of the sample is deprotein...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015816825920
更新日期：1991-02-01 00:00:00
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:Studies were conducted to investigate dilute solutions of the monoclonal antibody (mAb) bevacizumab, mAb fragment ranibizumab and fusion protein aflibercept, develop common procedures for formulation of low concentration mAbs and identify a stabilizing formulation for anti-VEGF mAbs for use in in vitro permeati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2368-7
更新日期：2018-02-28 00:00:00
abstract：PURPOSE:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodec...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2332-y
更新日期：2018-02-21 00:00:00
abstract：PURPOSE:The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS:Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9042-6
更新日期：2006-01-01 00:00:00
abstract：:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-007-9431-0
更新日期：2008-03-01 00:00:00
abstract：PURPOSE:A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1619-0
更新日期：2015-07-01 00:00:00
abstract：PURPOSE:The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subje...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1016275402723
更新日期：1995-12-01 00:00:00
abstract：PURPOSE:We examined the ability of a protein transduction domain (PTD), YARA, to penetrate in the skin and carry a conjugated peptide, P20. The results with YARA were compared to those of a well-known PTD (TAT) and a control, nontransducing peptide (YKAc). The combined action of PTDs and lipid penetration enhancers was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-2591-x
更新日期：2005-05-01 00:00:00
abstract：PURPOSE:To investigate the suitability of three antimicrobial peptides (AMPs) as cell-penetrating antimicrobial peptides. METHODS:Cellular uptake of three AMPs (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)-carboxytetramethylrhodamine-labeled, were tested in HeLa WT cells and analyzed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1550-9
更新日期：2015-05-01 00:00:00
abstract：PURPOSE:The purpose of this study was to establish a useful methodology, possibly providing information on the stoichiometry of pharmaceutical drug salts obtained from salt screening by using a multiwell plate and a Raman microscope. METHODS:Tamoxifen salt screening was conducted with monobasic and polybasic acids on ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9644-7
更新日期：2006-04-01 00:00:00
abstract：:An on-line simultaneous assay for the enantiomers of verapamil (VA) and its three metabolites in plasma was developed with column-switching HPLC. This system consists of an ovomucoid protein chiral stationary phase coupled to an achiral reversed-phase column via a dilution tube and a trapping column. The reversed-phas...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015848806240
更新日期：1991-08-01 00:00:00
abstract：:The effects of process and storage conditions of solid-state emulsions were studied. Oil-in-water emulsions may be prepared from solid state emulsions by adding an aqueous phase to the solid. Solid-state emulsions are prepared by processing an oil phase and an aqueous solution of matrix material via a solvent removal ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018983227234
更新日期：1993-07-01 00:00:00
abstract：PURPOSE:Levofloxacin, a quinolone antibacterial drug, is a zwitterion at physiological pH. We examined the effect of cationic and anionic drugs on renal excretion of levofloxacin by means of in vivo clearance to characterize the mechanisms of renal excretion of this drug. METHODS:In vivo clearance was studied in male ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012111902798
更新日期：1997-04-01 00:00:00
abstract：PURPOSE:To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. METHODS:Inhibition profiles for single Danshen components and combinations were generated in stably-ex...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1437-9
更新日期：2014-12-01 00:00:00
abstract：PURPOSE:An ex vivo intact toe model was developed to assess two different applicator designs for iontophoretic delivery of terbinafine into the nail only or the nail and surrounding skin. METHODS:Iontophoretic permeation studies were carried out on intact cadaver toes using nail-only and nail/skin applicators with a c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9934-y
更新日期：2009-09-01 00:00:00
