Abstract:
:PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing NH4Cl in the external phase to constrain DOX in dissolved polymer phase by suppressing DOX's inherent aqueous solubility as per common ion effect. This resulted in over 8-fold enhancement in entrapment efficiency of DOX inside BPNP, which otherwise is highly susceptible to leakage due to its relatively high aqueous solubility. TEM and DLS established BPNP to be sized below 100 nm, storage stability studies showed that BPNP were stable for one month at 4 °C, and in vitro release suggested significant control in drug release. Extensive in vitro and in vivo studies were conducted to propound anticancer and antiproliferative activity of BPNP. Plasma and tissue distribution study supplemented by pertinent in vivo fluorescence imaging mapped the exact fate of DOX contained inside BPNP once it was administered intravenously. A comparative safety profile via acute toxicity studies in mice was also generated to out rightly establish usefulness of BPNP. Results suggest that BPNP substantially enhance anticancer activity of DOX while simultaneously mitigating its toxic potential due to altered spatial and temporal presentation of drug and consequently deserve further allometric iteration.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Singh Y,Durga Rao Viswanadham KK,Kumar Jajoriya A,Meher JG,Raval K,Jaiswal S,Dewangan J,Bora HK,Rath SK,Lal J,Mishra DP,Chourasia MKdoi
10.1021/acs.molpharmaceut.7b00310subject
Has Abstractpub_date
2017-08-07 00:00:00pages
2749-2765issue
8eissn
1543-8384issn
1543-8392journal_volume
14pub_type
杂志文章abstract::Simvastatin is one of the most widely used active pharmaceutical ingredients for the treatment of hyperlipidemias. Because the compound is employed as a solid in drug formulations, particular attention should be given to the characterization of different polymorphs, their stability domains, and the nature of the phase...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00818
更新日期:2018-11-05 00:00:00
abstract::The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence following standard-of-care therapies, including surgical resection. With most tumors recurring near the site of surgical resection, local delivery of chemotherapy at the time of surgery is a promising strategy. Herein drug-loaded polymer s...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b01114
更新日期:2018-03-05 00:00:00
abstract::Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the e...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300496x
更新日期:2013-01-07 00:00:00
abstract::Within the immune system there is an exquisite ability to discriminate between "self" and "non-self" that is orchestrated by antigen-specific T lymphocytes. Genomic plasticity enables differentiation of naive CD4+ T lymphocytes into either regulatory cells (Treg) that express the transcription factor Foxp3 and activel...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100203a
更新日期:2011-02-07 00:00:00
abstract::The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300193f
更新日期:2012-10-01 00:00:00
abstract::Solid-state NMR (SSNMR) (1)H T1 and T1ρ relaxation times were used to evaluate the miscibility of amorphous solid dispersions of nifedipine (NIF) and polyvinylpyrrolidone (PVP) prepared by three different methods: melt quenching in the typical lab setting, spray drying and melt quenching in the NMR rotor while spinnin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400498n
更新日期:2014-01-06 00:00:00
abstract::Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles have a proven capacity for drug solubilization and have entered phase III clinical trials as a substitute for Cremophor EL in the delivery of paclitaxel in cancer therapy. PEG-b-PLA is less toxic than Cremophor EL, enabling a doubling of paclitaxel...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp2000549
更新日期:2011-08-01 00:00:00
abstract::Achieving effective gene therapy for glioma depends on gene delivery systems. The gene delivery system should be able to cross the blood-brain barrier (BBB) and further target glioma at its early stage. Active brain tumor targeted delivery can be achieved using the "Trojan horse" technology, which involves either endo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500084s
更新日期:2014-10-06 00:00:00
abstract::The present study explores the potential of polyelectrolyte-coated liposomes for improving the oral deliverability of doxorubicin (Dox). As a part of formulation strategy, stearyl amine was selected as a formulation component to provide positive charge to liposomes, which were subsequently coated with anionic poly(acr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300202c
更新日期:2012-09-04 00:00:00
abstract::The killing efficacy of doxorubicin from liposome-based delivery carriers has been shown to correlate strongly with its intracellular trafficking and, in particular, its fast and extensive release from the delivery carrier. However, previously explored pH-triggered mechanisms that were designed to become activated dur...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200079y
更新日期:2011-12-05 00:00:00
abstract::Tumor-associated inflammation has been linked to angiogenesis, metastasis and poor prognosis. The 18 kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR), is expressed in activated immune cells such as macrophages, but also in a number of cancer cell lines such as those of breast...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100433c
更新日期:2011-06-06 00:00:00
abstract::The adenovirus (Ad) is widely used as a vaccine because of its ability to induce a cellular and humoral immune response. In addition, human clinical trials have validated the safety and efficacy of Ad as a vaccine vector. The traditional approach for employing the adenovirus as vaccine is to configure the antigen gene...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/acs.molpharmaceut.8b00591
更新日期:2018-12-03 00:00:00
abstract::Myeloid differentiation primary response 88 (MyD88) is an intracellular adaptor protein central to the signaling of multiple receptors involved in inflammation. Since innate immune inflammation promotes autoimmunity, MyD88 is an attractive target in autoimmune disease. We previously developed c(MyD 4-4), a novel cycli...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01180
更新日期:2019-04-01 00:00:00
abstract::BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contri...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400485k
更新日期:2013-11-04 00:00:00
abstract::An ability to estimate the maximum flux of a xenobiotic across skin is desirable from the perspective of both drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This artic...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300146m
更新日期:2012-07-02 00:00:00
abstract::Process-induced phase transformations (PIPTs) of active pharmaceutical ingredients (APIs) can alter APIs' physicochemical properties and impact performance of pharmaceutical drug products. In this study, we investigated compression-induced amorphization of crystalline posaconazole (POSA), where the impact of mechanica...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01122
更新日期:2019-02-04 00:00:00
abstract::Despite holding promise for cancer immunotherapy, the strong pro-inflammatory properties of lipopolysaccharide (LPS) also account for severe localized and systemic side effects, restricting its administrable dosage and the possibility of chronic dosing. Herein, we exploited the surface-active properties of LPS molecul...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00631
更新日期:2019-11-04 00:00:00
abstract::Modifying nanoparticles with targeting peptides which can specifically bind to intestinal epithelium was recently suggested as a strategy to further enhance their ability for the oral delivery of macromolecular drugs. However, few studies were focused on comprehensive understanding of the uptake and transport processe...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400685v
更新日期:2014-05-05 00:00:00
abstract::The rapid absorptive clearance of drugs delivered to the airways of the lungs means that many inhaled medicines have a short duration of action. The aim of this study was to investigate whether forming polar ion-pairs can modify drug absorption to slow down clearance from the airways. Salbutamol was used as a model dr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01166
更新日期:2020-05-04 00:00:00
abstract::A combination of microbubbles (MBs) and ultrasound (US) is an emerging method for noninvasive and targeted enhancement of anti-cancer drug uptake. This method showed an increase local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models. The present study aims to evalu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00416
更新日期:2019-09-03 00:00:00
abstract::The purpose of this work was to elucidate the molecular interactions leading to monoclonal antibody self-association and precipitation and utilize biophysical measurements to predict solubility behavior at high protein concentration. Two monoclonal antibodies (mAb-G and mAb-R) binding to overlapping epitopes were inve...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00336
更新日期:2015-11-02 00:00:00
abstract::Intracellular unbound drug concentrations determine affinity to targets in the cell interior. However, due to difficulties in measuring them, they are often overlooked in pharmacology. Here we present a simple experimental technique for the determination of unbound intracellular drug concentrations in cultured cells t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4000822
更新日期:2013-06-03 00:00:00
abstract::Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)n, G5-(MFCO-MTX)n were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)n, D-(MFCO-MTX)n. The monomer G5-(COG-MTX)n conjugates exhibited only a weak, rapidly reversible binding...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500608s
更新日期:2014-11-03 00:00:00
abstract::Gene therapy represents a potential efficient approach of disease prevention and therapy. However, due to their poor in vivo stability, gene molecules need to be associated with delivery systems to overcome extracellular and intracellular barriers and allow access to the site of action. Cationic polymeric nanoparticle...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp5007213
更新日期:2015-02-02 00:00:00
abstract::The maytansinoid antibody-drug conjugates (ADCs) in clinical development for cancer therapy each contain a derivative of the microtubule-targeting agent, maytansine, covalently attached to the antibody via an engineered linker. A sample of any of these conjugates contains molecules with different numbers of maytansino...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5007536
更新日期:2015-06-01 00:00:00
abstract::By the combined use of powder and single-crystal X-ray diffraction, solid-state NMR, and molecular modeling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY, and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b01047
更新日期:2018-04-02 00:00:00
abstract::Organic anion-transporting polypeptides (OATPs) mediate the uptake of various drugs from blood into the liver in the basolateral membrane of hepatocytes. Positron emission tomography (PET) is a potentially powerful tool to assess the activity of hepatic OATPs in vivo, but its utility critically depends on the availabi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00588
更新日期:2018-10-01 00:00:00
abstract::Carbonic anhydrase IX (CAIX) plays an important role in glioma cell proliferation, invasion, metastasis, and resistance to radiotherapy and chemotherapy. An effective and noninvasive PET molecular imaging agent targeting CAIX would help its diagnosis and treatment but is not currently available. Recently, a low-molecu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01210
更新日期:2019-04-01 00:00:00
abstract::Metallacarborane moieties have been identified as promising pharmacophores. The pharmaceutical use of such compounds is, however, complicated by their low solubility and tendency to self-assemble in aqueous solution. In this work, we estimated the solubilities of a vast series of metallacarboranes [cobalt bis(dicarbol...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300565z
更新日期:2013-05-06 00:00:00
abstract::The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phot...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5001923
更新日期:2014-06-02 00:00:00