Abstract:
PURPOSE:Adjuvants are required to ensure the efficacy of subunit vaccines. Incorporating molecular immunopotentiators within particles could overcome drawbacks of molecular adjuvants (such as solubility and toxicity), and improve adjuvanticity of particles, achieving stronger adjuvant activity. Aim of this study is to evaluate the adjuvanticity of immunopotentiator-loaded polymeric particles for subunit vaccine. METHODS:PLGA microparticles (PMPs) and imiquimod (TLR-7 ligand)-loaded PLGA microparticles (IPMPs) were prepared by SPG premix membrane emulsification. In vitro and in vivo studies were performed to their adjuvant activity, using ovalbumin and H5N1 influenza split vaccine as antigens. RESULTS:Incorporating imiquimod into microparticles significantly improved the efficacy of PLGA microparticles in activating BMDCs and pMΦs, and antigen uptake by pMΦs was also promoted. IPMPs showed stronger adjuvanticity to augment OVA-specific immune responses than PMPs. IgG subclass profiles and cytokine secretion levels by splenocytes indicated that IPMPs elicited more Th1-polarized immune response, compared to PMPs. In vivo study using H5N1 influenza split vaccine as antigen also confirmed the effects of IPMPs on antigen-specific cellular immunity. CONCLUSIONS:Considering adjuvanticity and safety profiles (PLGA and IMQ, both approved by FDA), we conclude that IMQ-loaded PLGA microparticles are promising robust adjuvant for subunit vaccines.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Zhang W,Wang L,Yang T,Liu Y,Chen X,Liu Q,Jia J,Ma Gdoi
10.1007/s11095-015-1666-6subject
Has Abstractpub_date
2015-09-01 00:00:00pages
2837-50issue
9eissn
0724-8741issn
1573-904Xjournal_volume
32pub_type
杂志文章abstract:PURPOSE:The intratumoral heterogeneity observed in breast cancer (BC), in particular with regard to cell surface receptor expression, can hinder the success of many targeted cancer therapies. The development of novel therapeutic agents that target more than one receptor can overcome this inherent property of tumors and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2684-6
更新日期:2020-01-21 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:PURPOSE:Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gas...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016002606705
更新日期:1996-07-01 00:00:00
abstract::The binding of diflunisal to hydroxypropyl-beta-cyclodextrin (HP beta CD), bovine serum albumin (BSA), human serum albumin (HSA), normal human plasma, and mixed solutions of HP beta CD/protein was studied at 25 degrees C, pH 7.4, by potentiometry using an electrode selective to diflunisal. The experimental data for di...
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
abstract::Excessive production of reactive oxygen species by alveolar macrophages (AMs) in response to inhaled toxic substances is a major cause of oxidative lung injury. Therapeutic approaches designed to protect the lungs from oxidative injury by administering native antioxidant enzymes such as catalase and superoxide dismuta...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018976529766
更新日期:1994-08-01 00:00:00
abstract:PURPOSE:Gastroduodenal and intestinal permeability were compared after single doses of sustained release and regular release flurbiprofen in the rat to assess possible site-specific formulation-dependent toxicity. METHODS:Pharmacokinetics was assessed and gastrointestinal permeability was evaluated using sucrose and 5...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012134503107
更新日期:1997-11-01 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:[corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorptio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020412817716
更新日期:2002-10-01 00:00:00
abstract:PURPOSE:Ultrasound can be used to release a therapeutic payload encapsulated within a perfluorocarbon (PFC) emulsion via acoustic droplet vaporization (ADV), a process whereby the PFC phase is vaporized and the agent is released. ADV-generated microbubbles have been previously used to selectively occlude blood vessels ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0277-5
更新日期:2010-12-01 00:00:00
abstract::Leucine enkephalin (YGGFL) undergoes rapid degradation in sheep nasal mucosa to yield GGFL which is further degraded to FL. The activity of the nasal mucosal homogenate against YGGFL and GGFL (t1/2 12 and 7 min) was significantly greater than that observed with a nasal wash fluid (t1/2 40 and 13 min). The effect of cy...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018946829225
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:Evidence suggests that uremic toxins such as hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) promote the progression of renal failure by damaging tubular cells via rat organic anion transporter 1 (rOat1) and rOat3 on the basolateral membrane of ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-2486-x
更新日期:2005-04-01 00:00:00
abstract:PURPOSE:Hydrogen/deuterium (H/D) exchange over a range of temperatures suggests a protein structural/mobility transition in the solid state below the system glass transition temperature (Tg). The purpose of this study was to determine whether solid-state protein stability correlates with the difference between storage ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02897-7
更新日期:2020-08-13 00:00:00
abstract:PURPOSE:A conventional approach to assess cytochrome P450 (CYP) induction in preclinical animal models involves daily dosing for a least a week followed by Western blot and/or enzyme activity analysis. To evaluate the potential benefit of a third more specific and sensitive assay, real-time quantitative reverse transcr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025793707794
更新日期:2003-09-01 00:00:00
abstract:PURPOSE:To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2'-Azobis(-amidinopropane) dihydrochloride (AAPH). METHODS:AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solut...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-1199-x
更新日期:2005-02-01 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:PURPOSE:To develop a semi-physiological-based model describing simultaneously the time course of immature and mature B-lymphocytes after topotecan (TPT) administration to tumor-bearing rats. METHODS:Twenty-four tumor-bearing BDIX male rats received a single 6 mg/kg intra-peritoneal dose of TPT or saline. Mature and im...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-0025-x
更新日期:2010-03-01 00:00:00
abstract:PURPOSE:To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). METHODS:Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the sa...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1969-2
更新日期:2016-10-01 00:00:00
abstract::The transport characteristics of the renin inhibitor ((3S,4S)-4-[N-morpholinoacetyl-(1-naphthyl)-L-alanyl-N-methyl-(4-t hiazolyl)-L- alanyl]amino-3-hydroxy-5-cyclohexyl-1-(4-pyridyl)-1-pentanone; CH3-18) in rat small intestinal brush-border membrane vesicles (BBMV) were examined by a rapid filtration technique. The up...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018900124257
更新日期:1994-10-01 00:00:00
abstract:PURPOSE:Nasal delivery is a favorable route for vaccination against most respiratory infections, as antigen deposited in the nasal turbinate and Waldeyer's ring areas induce mucosal and systemic immune responses. However, little is known about the nasal distribution of the vaccines, specifically for infants. METHODS:A...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02976-9
更新日期:2021-01-15 00:00:00
abstract::A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transp...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016212804288
更新日期:1995-03-01 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::Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015902308676
更新日期:1990-12-01 00:00:00
abstract::Emulsions (o/w) were prepared from solid-state emulsions comprised of various matrix materials and oils and the resultant particle size properties determined. Results suggest that for those matrices that can form solid-state emulsions, the droplet size decreased as a function of time, as previously observed. The final...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018912100826
更新日期:1993-08-01 00:00:00
abstract:PURPOSE:Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for or...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0540-4
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochon...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0527-1
更新日期:2011-11-01 00:00:00
abstract::The bioavailability of dipyridamole, a poorly soluble weak base, was evaluated in 11 healthy, older subjects (> or = 65 years), 6 with a low fasting gastric pH (control) and 5 with a fasting gastric pH > 5 (achlorhydric), in a randomized, crossover design. Subjects received 50 mg dipyridamole as a single oral dose bot...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1018918316253
更新日期:1994-01-01 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:To evaluate the reaction of a large series of pharmacologically significant 1,4-dihydropyridine (1,4-DHP) compounds with superoxide (O2.-) in dimethylsulfoxide using differential pulse voltammetry and controlled potential electrolysis. METHODS:Differential pulse voltammetry was used to track the consumption of...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1022291624933
更新日期:2003-02-01 00:00:00
abstract:PURPOSE:We aimed to assess the fate of β-arteether lipid-based drug delivery systems (AE-LBDDS) in terms of resistance to lipolysis and permeation across intestinal cells. METHODS:AE-LBDDS contained Tween 80 or Cremophor EL as surfactants, ethanol, Maisine 35-1 and vegetable oil. The solubilization behavior of AE was ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1094-4
更新日期:2013-10-01 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