Abstract：
PURPOSE:Safe, targeted delivery of therapeutics remains a focus of drug/gene delivery, the aim being to achieve optimal efficacy while minimising off-target delivery. Dendrimers have a vast array of potential applications and have great potential as gene and drug delivery tools. We previously reported the development of peptide dendrimers that effectively complexed DNA and that have distinct advantages over conventional spherical dendrimers. Here, to expand the application of peptide-based low generation dendrimers we tested their capacity to be transformed into linkers for antibody-based targeting of diverse payloads. METHODS:Peptide-based low-generation asymmetric dendrimers were generated and conjugated to partially-reduced antibodies specific for B cell surface antigens or an irrelevant antigen. Preservation of antigen binding by the antibodies and targeting of the conjugated dendrimers carrying a small molecule (biotin) or plasmid DNA payloads was tested. RESULTS:Peptide-based low generation dendrimers were efficiently and site-specifically conjugated to antibodies with retention of antigen-binding capacity. Altering the branching termini of dendrimers facilitated delivery of diverse payloads in vitro and in vivo. CONCLUSIONS:We propose that safe, non-toxic peptide dendrimers, which are readily synthesised and modifiable for a variety of applications, form the basis of a new family of biocompatible "linkers" with substantial potential for targeted delivery applications.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Shah ND,Parekh HS,Steptoe RJdoi
10.1007/s11095-014-1408-1subject
Has Abstractpub_date
2014-11-01 00:00:00pages
3150-60issue
11eissn
0724-8741issn
1573-904Xjournal_volume
31pub_type
杂志文章abstract：PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2743-z
更新日期：2020-01-08 00:00:00
abstract：PURPOSE:To evaluate the mechanism of renal transport of quinolone antibacterial drugs, we examined the interaction of levofloxacin with p-aminohippurate (PAH) transport systems and the transport of levofloxacin in renal epithelial cells. METHODS:Transport of [14C]PAH or [14C]levofloxacin was measured using OK cell mon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011012822437
更新日期：2001-05-01 00:00:00
abstract：:Indomethacin microspheres based on a combination of ethylcellulose and polyethyleneglycol were prepared using the solvent evaporation process. Release profiles of ensemble and individual microspheres were measured. Both were found to follow first-order kinetics, in contrast to what was expected. This was attributed to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015917023949
更新日期：1988-03-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. METHODS:Human recombinant IFN-alpha was given to rats (n = 5-7 per group...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7415-5
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:The gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared for gadolinium neutron-capture therapy (Gd-NCT) and characterized and evaluated as a device for intratumoral (i.t.) injection. METHODS:Gd-nanoCPs were prepared by a novel emulsion-droplet coalescence technique. The effects...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018995124527
更新日期：1999-12-01 00:00:00
abstract：PURPOSE:Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012161630481
更新日期：1997-08-01 00:00:00
abstract：PURPOSE:To provide a systematic biophysical approach towards a better understanding of impact of conjugation chemistry on higher order structure and physical stability of an antibody drug conjugate (ADC). METHODS:ADC was prepared using thiol-maleimide chemistry. Physical stabilities of ADC and its parent IgG1 mAb were...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1274-2
更新日期：2014-07-01 00:00:00
abstract：PURPOSE:To measure the diffusion of nanometer polymersomes through tissue engineered human oral mucosa. METHODS:In vitro models of full thickness tissue engineered oral mucosa (TEOM) were used to assess the penetration properties of two chemically different polymersomes comprising two of block copolymers, PMPC-PDPA an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9882-6
更新日期：2009-07-01 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:To develop an efficient tumor vasculature-targeted polymeric micelle delivery system for combretastatin A4 (CA4), a novel antivascular agent. METHODS:CA4-loaded micelles were prepared from poly (ethylene glycol)-b-poly (d, l-lactide) copolymers. RGD peptides that target integrins alphavbeta3 and alphavbeta5, m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0184-9
更新日期：2010-09-01 00:00:00
abstract：:Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led t...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-008-9634-z
更新日期：2008-12-01 00:00:00
abstract：:The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair fo...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015963128124
更新日期：1989-09-01 00:00:00
abstract：PURPOSE:To develop a liposomal system with high drug loading (DL) for intravenous (i.v.) delivery of a poorly water-soluble basic drug, asulacrine (ASL). METHODS:A thin-film hydration and extrusion method was used to fabricate the PEGylated liposomal membranes followed by a freeze and thaw process. A novel active drug...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1551-8
更新日期：2015-04-01 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：PURPOSE:Study on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers. METHODS:The concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2643-2
更新日期：2019-06-03 00:00:00
abstract：PURPOSE:To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS:Caco...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011032502097
更新日期：2001-02-01 00:00:00
abstract：PURPOSE:Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2244-x
更新日期：2017-11-01 00:00:00
abstract：PURPOSE:To investigate the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate (FP) for carrier based dry powder inhaler (DPI) formulations. METHODS:Young's modulus of FP crystals produced using different anti-solvents was determined...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0640-1
更新日期：2012-04-01 00:00:00
abstract：PURPOSE:This paper attempts to correlate the hydrophobic contribution constants (faa) of 21 amino acids in small peptides with commonly used physiochemical parameters. These faa constants can then be used to predict hydrophobicity change in peptides when any one of the amino acid residue is substituted with another. M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016008102587
更新日期：1996-08-01 00:00:00
abstract：PURPOSE:The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS:These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), ...
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: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: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:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016225707807
更新日期：1995-09-01 00:00:00
abstract：PURPOSE:To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. METHODS:Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/kg), serial collection of arterial bloo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011973409022
更新日期：1998-01-01 00:00:00
abstract：PURPOSE:The purpose of this work was to determine the jejunal permeability of cyclosporin A (CsA) in humans and whether formulation variables modulate the effects of P-glycoprotein (P-gp) on the permeability of CsA in Caco-2 cells. METHODS:A solution containing CsA, phenylalanine, propranolol, polyethyleneglycol (PEG)...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023481418576
更新日期：2003-05-01 00:00:00
abstract：PURPOSE:The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. METHODS:Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1861-0
更新日期：2016-05-01 00:00:00
abstract：:Various derivatives of the C-terminal amide group in N-protected amino acid and peptide amides were synthesized to assess their suitability as prodrug forms with the aim of protecting the amide or peptide bond against cleavage by alpha-chymotrypsin. Whereas N-acetylation, N-hydroxymethylation, and N-phthalidylation di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015854718903
更新日期：1991-12-01 00:00:00
abstract：PURPOSE:To describe a computational tool to calculate molecular descriptors of potential application in ADME virtual screening of antitumor Pt(II) drug candidates. METHODS:The multistep computational procedure consists in (a) building and optimization (PM3) of the 3D structures of the investigated complexes, (b) param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0317-1
更新日期：2011-03-01 00:00:00
abstract：PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8815-2
更新日期：2006-01-01 00:00:00
abstract：PURPOSE:The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD:The shape of the crystals was changed by polymorphic transformation of o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020492213172
更新日期：2002-10-01 00:00:00
