Abstract：
PURPOSE:Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile. METHODS:We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using matrix IVRs containing IQP-0528, a poorly soluble but highly potent antiretroviral drug with an IC90 of 146 ng/mL. These IVRs consisted of drug-loaded segments, 15.6% IQP-0528 in Tecoflex 85A, comprising either all, half, or a quarter of the entire ring. RESULTS:In vitro release under sink conditions demonstrates loading-proportional release, with a cumulative 30-day release of 48.5 ± 2.2 mg for our 100% loaded ring, 24.8 ± .36 mg from our 50% loaded ring, and 13.99 ± 1.58 mg from our 25% loaded ring. In vivo, while drug concentration in vaginal fluid is well in excess of IQP-0528's EC90, we find no statistical difference between the different ring loadings in either swab drug levels or drug released from our rings. CONCLUSIONS:We show that in vitro release may not accurately reflect in vivo release, particularly for poorly soluble drugs. All tested loadings of our IVRs are capable of delivering IQP-0528 well in excess of the IC90.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Su JT,Teller RS,Srinivasan P,Zhang J,Martin A,Sung S,Smith JM,Kiser PFdoi
10.1007/s11095-017-2224-1subject
Has Abstractpub_date
2017-10-01 00:00:00pages
2163-2171issue
10eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-017-2224-1journal_volume
34pub_type
杂志文章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:To investigate the possible pathways for transport of wheat germ agglutinin conjugated PEG-PLA nanoparticles (WGA-NP) into the brain after nasal administration. METHODS:The nose-to-brain pathways were investigated using WGA-NP containing 6-coumarin (as a fluorescent marker) and (125)I-labeled WGA-NP. Ex vivo i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0641-0
更新日期：2012-02-01 00:00:00
abstract：:The immune system has the ability to recognize and kill pre-cancer and cancer cells. However, with the immune system's surveillance, the survival tumor cells learn how to escape the immune system after immunoselection. Cancer immunotherapy develops strategies to overcome these problems. Nanomedicine applications in ca...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-010-0258-8
更新日期：2011-02-01 00:00:00
abstract：PURPOSE:To evaluate micronized powder retention and detachment from inhaler surfaces following reproducible deposition by impaction, coupled with centrifugal particle detachment (CPD). METHODS:Micronized albuterol sulfate (AS) and beclomethasone dipropionate (BDP) were aerosolized as dry powders and deposited by casca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014451203619
更新日期：2002-03-01 00:00:00
abstract：PURPOSE:Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compou...
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：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：PURPOSE:Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To addre...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0190-y
更新日期：2010-09-01 00:00:00
abstract：:The internalization of a neuromodulatory adrenocorticotropic hormone (ACTH) analogue, [125I]ebiratide (H-Met(O2)-Glu[125I]His-Phe-D-Lys-Phe-NH(CH2)2NH2), was examined in cultured monolayers of bovine brain capillary endothelial cells (BCEC). HPLC analysis of the incubation solution showed that [125I]ebiratide was not ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015848531603
更新日期：1992-04-01 00:00:00
abstract：PURPOSE:To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. METHODS:Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a d...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022652004114
更新日期：2003-03-01 00:00:00
abstract：PURPOSE:Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0459-9
更新日期：2011-09-01 00:00:00
abstract：PURPOSE:Cell penetrating peptides (CPPs) were widely used as motifs for drug delivery to tumor. In former study, an RGD reverse sequence dGR was used to develop active-targeting liposome R8dGR-Lip, which showed well penetrating ability and treatment efficiency on glioma model. However, recurrence after tumor resection ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2399-0
更新日期：2018-04-26 00:00:00
abstract：PURPOSE:Iontophoresis was employed for enhancing the transdermal delivery of acyclovir through nude mouse skin in vitro, with the aim of understanding the mechanisms responsible for drug transport, in order to properly set the conditions of therapeutical application. METHODS:Experiments were done in horizontal diffusi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016284815501
更新日期：1995-11-01 00:00:00
abstract：PURPOSE:To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity. METHODS:Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9674-4
更新日期：2008-11-01 00:00:00
abstract：PURPOSE:To study the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for recombinant tuberculosis (TB) antigen, TB10.4-Ag85B, with the ultimate goal of pulmonary delivery as vaccine for the prevention of TB. MATERIALS AND METHODS:Recombinant TB antigens were purified from E. co...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0028-7
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis (RA). Our aim was to apply a model-informed drug development (MIDD) approach to examine the totality of available clinical efficacy data. METHODS:Population pha...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2752-y
更新日期：2020-01-06 00:00:00
abstract：PURPOSE:Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02929-2
更新日期：2020-09-28 00:00:00
abstract：PURPOSE:To investigate whether conjunctival epithelial cells express transport processes for opioid peptides. METHODS:We monitored the uptake of [(3)H]deltorphin II and [(3)H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9709-x
更新日期：2009-05-01 00:00:00
abstract：PURPOSE:To examine the theoretical/practical utility of the liver-to-blood partition coefficient (Kpuu) for predicting drug-drug interactions (DDIs), and compare the Kpuu-approach to the extended clearance concept AUCR-approach. METHODS:The Kpuu relationship was derived from first principles. Theoretical simulations i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02797-w
更新日期：2020-03-25 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
doi：10.1007/s11095-007-9347-8
更新日期：2008-03-01 00:00:00
abstract：:Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015982204926
更新日期：1989-08-01 00:00:00
abstract：PURPOSE:The purpose of the present study is to explore whether a poly-L-arginine (poly-L-Arg)-induced increase in tight junctions (TJ) permeability of fluorescein isothiocyanate-labeled dextran (MW 4.4 kDa, FD-4) is associated with the Ca2+-dependent signaling and occurs following the phosphorylation/dephosphorylation ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000003383.86238.d1
更新日期：2003-11-01 00:00:00
abstract：PURPOSE:A Selegiline Transdermal System (STS) is under development for indications which may not be optimally or safely treated with oral selegiline. Studies were conducted to evaluate the in vitro penetration and skin metabolism of selegiline in order to better understand the toxicological findings and the observed pl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012051300130
更新日期：1997-01-01 00:00:00
abstract：PURPOSE:For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery ca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020769716288
更新日期：2002-11-01 00:00:00
abstract：:A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018929531410
更新日期：1993-04-01 00:00:00
abstract：PURPOSE:To study Cereport (RMP-7, bradykinin B2 agonist) effects on human brain microvascular endothelial cell (HBMEC) monolayer permeability. METHODS:HBMEC grown on transwell membranes were exposed to Cereport. The monolayer permeability was determined with [14C]-inulin (MW. 5,200) and [3H]-dextran (MW. 70,000). RES...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018938722768
更新日期：1999-09-01 00:00:00
abstract：:Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the in...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-2043-9
更新日期：2017-02-01 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：:A novel method of dipeptide synthesis is described that can be carried out in aqueous solution and does not require complicated protecting and deprotecting procedures. An analgesic neuropeptide named kyotorphin, H-Tyr-Arg-OH, was synthesized from unprotected tyrosine and arginine in a new enzymatic reaction catalyzed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016479305603
更新日期：1987-04-01 00:00:00
abstract：PURPOSE:Short linear peptides have a high potential for delivering various drugs with therapeutic potential, including nucleic acids. Recently, we have shown that the cationic amphipathic histidine-rich peptide LAH4 (KKALLALALHHLAHLALHLALALKKA) possesses high plasmid DNA delivery capacities. Since such peptides are tho...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0138-2
更新日期：2010-07-01 00:00:00
abstract：PURPOSE:For the assessment of bioequivalence it is assumed that drug clearance in each subject on each of the study days is the same and any observed differences in AUC and/or Cmax between a brand and generic formulation are due to differences in bioavailability. We hypothesized that this assumption was invalid for hig...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1016040825844
更新日期：1996-06-01 00:00:00
