Study and Characterization of TM sub ono Cylindrical Resonant Cavity Combiners

Allen, D.L.

doi:10.21236/ada100491

Cited by 6 publications

(8 citation statements)

References 2 publications

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“…[1][2][3] Most of these enhancements derive from the difference in size of polymer micelles relative to their small molecule encapsulates and from the biocompatibility imparted by their hydrophilic polymer shells. 4 Since the 1990s, numerous polymer assemblies have been developed to deliver assorted payloads, including small molecule anticancer drugs, [5][6] contrast/imaging agents, [7][8] proteins, 9 RNA, 10 and DNA, 11 among others.…”

Section: Introductionmentioning

confidence: 99%

Tuning H₂S Release by Controlling Mobility in a Micelle Core

et al. 2019

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Drug delivery from polymer micelles has been widely studied, but methods to precisely tune rates of drug release from micelles are limited. Here, the mobility of hydrophobic micelle cores was varied to tune the rate at which a covalently bound drug was released. This concept was applied to cysteine-triggered release of hydrogen sulfide (H 2 S), a signaling gas with therapeutic potential. In this system, thiol-triggered H 2 S donor molecules were covalently linked to the hydrophobic blocks of self-assembled polymer amphiphiles. Because release of H 2 S is triggered by cysteine, diffusion of cysteine into the hydrophobic micelle core was hypothesized to control the rate of release. We confirmed this hypothesis by carrying out release experiments from H 2 S-releasing micelles in varying compositions of EtOH/H 2 O. Higher EtOH concentrations caused the micelles to swell, facilitating diffusion in and out of their hydrophobic cores and leading to faster H 2 S release from the micelles. To achieve a similar effect without addition of organic solvent, we prepared micelles with varying core mobility via incorporation of a plasticizing co-monomer in the core-forming block. The glass transition temperature (T g ) of the core block could therefore be precisely varied by changing the amount of the plasticizing co-monomer in the polymer. In aqueous solution under identical conditions, the release rate of H 2 S varied over 20-fold (t ½ = 0.18 -4.2 h), with the lowest T g hydrophobic block resulting in the fastest H 2 S release. This method of modulating release kinetics from polymer micelles by tuning core mobility may be applicable to many types of physically encapsulated and covalently linked small molecules in a variety of drug delivery systems.

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Section: Introductionmentioning

confidence: 99%

Tuning H₂S Release by Controlling Mobility in a Micelle Core

et al. 2019

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“…[45][46][47][48] Because the vesicle size was less than 250 nm, these liposomes are unlikely to be phagocytosed by alveolar macrophages and thus they can escape lung clearance mechanism and dwell longer in the lungs. 29,49 Colloidal stability for liposomal formulations is important because any instability may adversely affect the hydrodynamic diameter and thus affect the extent and mechanism of cellular uptake. 50 Large negative zeta potential of our particles offers protection against aggregation due to mutual electrostatic repulsive forces, which keeps particle separated and helps prevent coalescence.…”

Section: Discussionmentioning

confidence: 99%

CAR, a Homing Peptide, Prolongs Pulmonary Preferential Vasodilation by Increasing Pulmonary Retention and Reducing Systemic Absorption of Liposomal Fasudil

et al. 2019

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Here, we sought to elucidate the role of CAR (a cyclic peptide) in the accumulation and distribution of fasudil, a drug for pulmonary arterial hypertension (PAH), in rat lungs and in producing pulmonary specific vasodilation in PAH rats. As such, we prepared liposomes of fasudil and CAR-conjugated liposomal fasudil and assessed the liposomes for CAR conjugation, physical properties, entrapment efficiencies, in vitro release profiles, and stabilities upon incubation in cell culture media, storage, and aerosolization. We also studied the cellular uptake of fasudil in different formulations, quantified heparan sulfate (HS) in pulmonary arterial smooth muscle cells (PASMCs), and investigated the distribution of the liposomes in the lungs of PAH rats. We assessed the drug accumulation in a close and recirculating isolated perfused rat lung model and studied the pharmacokinetics and pharmacological efficacy of the drug and formulations in Sugen/ hypoxia-induced PAH rats. The entrapment efficiency of the liposomal fasudil was 95.5 ± 4.5%, and the cumulative release was 93.95 ± 6.22%. The uptake of CAR liposomes by pulmonary arterial cells and their distribution and accumulation in the lungs were much greater than those of no-CAR-liposomes. CAR-induced increase in the cellular uptake was associated with an increase in HS expression by rat PAH-PASMCs. CAR, when conjugated with liposomal fasudil and given via an intratracheal instillation, extended the elimination half-life of the drug by four-fold compared with fasudil-in-no-CAR-liposomes given via the same route. CAR-conjugated liposomal fasudil, as opposed to fasudil-in-no-CAR-liposomes and CAR pretreatment followed by *

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“…Liposome, a lipid based spherical bilayered particle, is considered as an attractive delivery agent due to its biocompatibility, biodegradability and controlled release property. 105 Significant research efforts have been made to design liposomes that can be sensitive to stimuli (pH 106 , redox 107 , light 108 , temperature 109 ), have long circulation half-life (PEGylation 110 ) and can even be decorated with ligands/antibodies for specific targeting. 111 Understandably, the desirable aspects of this platform has led to commercial development of several therapeutics (Doxil/Caelix-Johnson & Johnson, AmBisome-Gilead, Myocet-Cephalon).…”

Section: Liposomal Deliverymentioning

confidence: 99%

“…111 Understandably, the desirable aspects of this platform has led to commercial development of several therapeutics (Doxil/Caelix-Johnson & Johnson, AmBisome-Gilead, Myocet-Cephalon). 105 Within the area of antibody delivery (Table 1), a cationic liposome, PULSin (Polyplustransfection (Illkirch, France)) was utilized to deliver mouse-IgG, anti-transmembrane golgi protein giantin and anti-nuclear pore complex in HeLa cells. 112 In another study, a liposomal formulation was prepared with cationic trifluoroacetylated lipopolyamine (TFA-DODAPL) and neutral dioleoyl phosphatidylethanolamine (DOPE) combination (TFA-DODAPL:DOPE= 2:1, called BioPORTER, Gene Therapy Systems, San Diego, CA) to deliver functional proteins and a fluorescent antibody (FITC-IgG) into cytoplasm of five different cell types.…”

Section: Liposomal Deliverymentioning

confidence: 99%

Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

et al. 2019

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Proteins have sparked fast growing interest as biological therapeutic agents for several diseases. Antibodies, in particular, carry an enormous potential as drugs owing to their remarkable target specificity and low immunogenicity. Although the market has numerous antibodies directed towards extracellular targets, their use in targeting therapeutically important intracellular targets is limited by their inability to cross cellular membrane. Realizing the potential for antibody therapy in disease treatment, progress has been made in the development of methods to deliver antibodies intracellularly. In this review, we address various platforms for delivery of antibodies, their merits and drawbacks.

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Study and Characterization of TM sub ono Cylindrical Resonant Cavity Combiners

Cited by 6 publications

References 2 publications

Tuning H₂S Release by Controlling Mobility in a Micelle Core

Tuning H₂S Release by Controlling Mobility in a Micelle Core

CAR, a Homing Peptide, Prolongs Pulmonary Preferential Vasodilation by Increasing Pulmonary Retention and Reducing Systemic Absorption of Liposomal Fasudil

Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

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Study and Characterization of TM sub ono Cylindrical Resonant Cavity Combiners

Cited by 6 publications

References 2 publications

Tuning H2S Release by Controlling Mobility in a Micelle Core

Tuning H2S Release by Controlling Mobility in a Micelle Core

CAR, a Homing Peptide, Prolongs Pulmonary Preferential Vasodilation by Increasing Pulmonary Retention and Reducing Systemic Absorption of Liposomal Fasudil

Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

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Tuning H₂S Release by Controlling Mobility in a Micelle Core

Tuning H₂S Release by Controlling Mobility in a Micelle Core