Abstract:
:Current chemotherapy strategies for second-line treatment of relapsed ovarian cancer are unable to effectively treat residual disease post-cytoreduction. The findings presented herein suggest that tissue penetration of drug is not only an issue for large, unresectable tumors, but also for invisible, microscopic lesions. The present study sought to investigate the potential of a block copolymer micelle (BCM) formulation, which may reduce toxicities of doxorubicin (DOX) in a similar way to pegylated liposomal doxorubicin (PLD, Doxil/Caelyx), while enhancing penetration into tumor tissue and improving intratumoral availability of drug. To achieve this goal, 50 nm-sized BCMs capable of high DOX encapsulation (BCM-DOX) at drug levels ranging from 2 to 7.6 mg/mL were formulated using an ultrafiltration technique. BCM-DOX was evaluated in 2D and 3D cell culture of the human ovarian cancer cell lines HEYA8, OV-90, and SKOV3. Additionally, the current study examines the impact of mild hyperthermia (MHT) on the cytotoxicity of DOX. The BCM-DOX formulation fulfilled the goal of controlling drug release while providing up to 9-fold greater cell monolayer cytotoxicity in comparison to PLD. In 3D cell culture, using multicellular tumor spheroids (MCTS) as a model of residual disease postsurgery, BCM-DOX achieved the benefits of an extended release formulation of DOX and resulted in improvements in drug accumulation over PLD, while yielding drug levels approaching that achievable by exposure to DOX alone. In comparison to PLD, this translated into superior MCTS growth inhibition in the short term and comparable inhibition in the long term. Overall, although MHT appeared to enhance drug accumulation in HEYA8 MCTS treated with BCM-DOX and DOX alone in the short term, improved growth inhibition of MCTS by MHT was not observed after 48 h of drug treatment. Evaluation of BCM-DOX in comparison to PLD as well as the effects of MHT is warranted in vivo.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Eetezadi S,De Souza R,Vythilingam M,Lessa Cataldi R,Allen Cdoi
10.1021/acs.molpharmaceut.5b00426subject
Has Abstractpub_date
2015-11-02 00:00:00pages
3973-85issue
11eissn
1543-8384issn
1543-8392journal_volume
12pub_type
杂志文章abstract::The endothelial cells lining the capillaries supplying the brain with oxygen and nutrients form a formidable barrier known as the blood-brain barrier (BBB), which exhibits selective permeability to small drug molecules and virtually impermeable to macromolecular therapeutics. Current in vitro BBB models fail to replic...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00805
更新日期:2016-03-07 00:00:00
abstract::A novel design of anticancer drug delivery system, based on an electrostatic binding of negatively charged liposomes and cationic metalloporphyrins under physiological conditions, is reported. A lack of cytotoxicity of the iron(III) porphyrin-loaded liposomes and an efficient generation of a toxic hydroxyl radical (OH...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp049936v
更新日期:2004-09-01 00:00:00
abstract::5P12-RANTES is a recently developed chemokine analogue that has shown high level protection from SHIV infection in macaques. However, the feasibility of using 5P12-RANTES as a long-term HIV prevention agent has not been explored partially due to the lack of available delivery devices that can easily be modified for lo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3007242
更新日期:2013-10-07 00:00:00
abstract::Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin: the stratum corneum (SC) and tight junctions. We have previously reporte...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00997
更新日期:2021-01-04 00:00:00
abstract::Macromolecules with defined nanosizes--nanoglobules--were synthesized and characterized as novel drug carriers with precise molecular architectures. Poly-L-lysine dendrimers with a cubic octa(3-aminopropyl)silsesquioxane (OAS) core, (L-lysine 8-OAS, (L-lysine) 16-(L-lysine) 8-OAS, (L-lysine) 32-(L-lysine) 16-(L-lysine...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp070036z
更新日期:2007-09-01 00:00:00
abstract::The transfer of genetic material into cells using nonviral vectors offers unique potential for therapeutics; however, the efficacy of delivery depends upon a poorly understood, multistep pathway, limiting the prospects for successful gene delivery. Mechanistic insight into DNA association and release has been hampered...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3002864
更新日期:2012-09-04 00:00:00
abstract::Retinal pigment epithelium, which forms the outer blood-retinal barrier, is a critical barrier for transport of drugs to the retina. The purpose of this study was to develop a pigmented MDCK (P-MDCK) cell line as a rapidly established in vitro model for the outer blood-retinal barrier to assess the influence of melani...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300305f
更新日期:2012-11-05 00:00:00
abstract::Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs posse...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00670
更新日期:2016-04-04 00:00:00
abstract::Platinum(IV) complexes generally require reduction to reactive Pt(II) species to exert their chemotherapeutic activity. The process of reductive activation of (15)N-labeled (OC-6-43)-bis(acetato)diamminedichloridoplatinum(IV), in the presence of nicotinamide adenine dinucleotide (NADH) and horse heart cytochrome c (cy...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00438
更新日期:2016-09-06 00:00:00
abstract::Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average partic...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500723k
更新日期:2015-02-02 00:00:00
abstract::The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide)...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00195
更新日期:2019-06-03 00:00:00
abstract::Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two O...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00129
更新日期:2016-05-02 00:00:00
abstract::Saquinavir mesylate (SQV) is the first-in-class and prototypical HIV protease inhibitor (PI) used in the treatment of HIV infection. SQV undergoes extensive hepatic metabolism and intestinal and bile secretion, and has poor and variable oral bioavailability. In previous studies, our group and others have described the...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp0340136
更新日期:2004-01-12 00:00:00
abstract::Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00904
更新日期:2019-01-07 00:00:00
abstract::It is well established that polymers adopt a range of conformations and solution-state organization in response to varying solution environments, although very little work has been done to understand how these effects might impact the physical stability and bioavailability of spray-dried amorphous dispersions (SDDs). ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00729
更新日期:2020-12-07 00:00:00
abstract::The controversy surrounding the use of diphtheria toxin (DT) as a therapeutic agent against tumor cells arises mainly from its unexpected harmfulness to healthy tissues. We encoded the cytotoxic fragment A of DT (DTA) as an objective gene in the Light-On gene-expression system to construct plasmids pGAVPO (pG) and pU5...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01038
更新日期:2020-01-06 00:00:00
abstract::Similar to glycolysis, glutaminolysis acts as a vital energy source in tumor cells, providing building blocks for the metabolic needs of tumor cells. To capture glutaminolysis in tumors, 18F-(2S,4R)4-fluoroglutamine ([18F]FGln) and 18F-fluoroboronoglutamine ([18F]FBQ) have been successfully developed for positron emis...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00891
更新日期:2019-12-02 00:00:00
abstract::Peptide nucleic acids have a number of features that make them an ideal platform for the development of in vitro biological probes and tools. Unfortunately, their inability to pass through membranes has limited their in vivo application as diagnostic and therapeutic agents. Herein, we describe the development of catio...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp800199w
更新日期:2009-03-01 00:00:00
abstract::Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the i...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp0600541
更新日期:2006-09-01 00:00:00
abstract::Hydrophobic single-wall carbon nanohorns (SWNHs) were dispersed in aqueous media by noncovalently modifying their surfaces with conjugate molecules comprised of polyethylene glycol (PEG) and a peptide aptamer (NHBP-1) that specifically bind to the surfaces of the SWNHs. The conjugates were synthesized by coupling PEG ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp070022t
更新日期:2007-09-01 00:00:00
abstract::In the present age of pharmaceutical research and development, focused delivery of decision making data is more imperative than ever before. Resulting from several years' success, failure and consequential learning, this article also proffers advice and guidance on which in vitro and in vivo experiments to perform to ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300476z
更新日期:2013-04-01 00:00:00
abstract::In this work we measured self-diffusion coefficients of 5 drugs (aspirin, caffeine, ethionamide, salicylic acid, and paracetamol) and 11 biologically active compounds of similar structure in deuterated water and 1-octanol by NMR. It has been found that an increase in the van der Waals volume of the molecules of the st...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00401
更新日期:2017-10-02 00:00:00
abstract::There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00669
更新日期:2017-12-04 00:00:00
abstract::The objective was to determine the disposition of polymer nanoparticles and an associated, lipophilic, model "active" component on and within the skin following topical application. Polystyrene and poly(methyl methacrylate) nanoparticles containing covalently bound fluorescein methacrylate and dispersed Nile Red were ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp9001188
更新日期:2009-09-01 00:00:00
abstract::Olive pollen is one of the most important causes of respiratory allergy, with Ole e 1 being the most clinically relevant sensitizing allergen. Peptide-based vaccines represent promising therapeutic approaches, but the use of adjuvants is required to strengthen the weak immunogenicity of small peptides. We propose the ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01082
更新日期:2020-03-02 00:00:00
abstract::2-Methoxyestradiol (2MeO-E2) is an endogenous metabolite of estrogen which was initially considered to be inactive. During the last few decades it has been shown that 2MeO-E2 is a promising anticancer drug. In vitro experiments have demonstrated that it has several anticancer activities, and potential to alleviate hyp...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp100190f
更新日期:2010-12-06 00:00:00
abstract::The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viabil...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4005035
更新日期:2014-02-03 00:00:00
abstract::Drug transporter expression and function at the blood-brain barrier is altered in Alzheimer's disease (AD). However, the impact of AD on the expression of transporters and metabolizing enzymes in peripheral tissues has received little attention. The current study evaluated the expression of drug transporters and metab...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00500
更新日期:2018-09-04 00:00:00
abstract::In this study, the polymer-free electrospinning was performed in order to produce cyclodextrin/ibuprofen inclusion complex nanofibers, which could have potential as the fast dissolving oral drug delivery system. Ibuprofen is a poorly water-soluble nonsteroidal anti-inflammatory drug; however, the water solubility of i...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00798
更新日期:2019-10-07 00:00:00
abstract::Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the anticonvulsant phenytoin sodium can promote reepithelization of corneal ulcers as it was repurposed for skin wound ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00742
更新日期:2020-10-05 00:00:00