The Experts below are selected from a list of 26103 Experts worldwide ranked by ideXlab platform
Alexander V. Kabanov - One of the best experts on this subject based on the ideXlab platform.
-
Pluronics and MDR reversal: an update.
Molecular Pharmaceutics, 2014Co-Authors: Daria Y. Alakhova, Alexander V. KabanovAbstract:Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers. Triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in a triblock structure PEO-PPO-PEO, Pluronics or “poloxamers”, raised a considerable interest in the drug delivery field. Previous studies demonstrated that Pluronics sensitize MDR cancer cells resulting in increased cytotoxic activity of Dox, paclitaxel, and other drugs by 2–3 orders of magnitude. Pluronics can also prevent the development of MDR in vitro and in vivo. Additionally, promising results of clinical studies of Dox/Pluronic formulation reinforced the need to ascertain a thorough understanding of Pluronic effects in tumors. These effects are extremely comprehensive and...
-
Pluronic block copolymers evolution of drug delivery concept from inert nanocarriers to biological response modifiers
Journal of Controlled Release, 2008Co-Authors: Elena V Batrakova, Alexander V. KabanovAbstract:Polymer nanomaterials have sparked a considerable interest as vehicles used for diagnostic and therapeutic agents; research in nanomedicine has not only become a frontier movement but is also a revolutionizing drug delivery field. A common approach for building a drug delivery system is to incorporate the drug within the nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. With this foundation, nanoparticles with stealth properties that can circumvent RES and other clearance and defense mechanisms are the most promising. However, recent developments indicate that select polymer nanomaterials can implement more than only inert carrier functions by being biological response modifiers. One representative of such materials is Pluronic block copolymers that cause various functional alterations in cells. The key attribute for the biological activity of Pluronics is their ability to incorporate into membranes followed by subsequent translocation into the cells and affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, apoptotic signal transduction, and gene expression. As a result, Pluronics cause drastic sensitization of MDR tumors to various anticancer agents, enhance drug transport across the blood brain and intestinal barriers, and causes transcriptional activation of gene expression both in vitro and in vivo. Collectively, these studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent field of nanomedicine.
-
effect of Pluronic p85 on atpase activity of drug efflux transporters
Pharmaceutical Research, 2004Co-Authors: Elena V Batrakova, Shu Li, Yili Li, Valery Alakhov, Alexander V. KabanovAbstract:Purpose. Pluronic block copolymers are potent sensitizers of multidrug resistant (MDR) cancer cells. The sensitization effect by Pluronics is a result of two processes acting in concert: i) intracellular ATP depletion, and ii) inhibition of ATPase activity of drug efflux proteins. This work characterizes effects of Pluronic P85 on ATPase activities of Pgp, MRP1, and MRP2 drug efflux transport proteins and interaction of these proteins with their substrates, vinblastine, and leucotriene C4.
-
optimal structure requirements for Pluronic block copolymers in modifying p glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Elena V Batrakova, Shu Li, Valery Alakhov, Donald W Miller, Alexander V. KabanovAbstract:Pluronic block copolymer P85 was shown to inhibit the P-glycoprotein (Pgp) drug efflux system and to increase the permeability of a broad spectrum of drugs in the blood-brain barrier (BBB). However, there is an entire series of Pluronics varying in lengths of propylene oxide and ethylene oxide and overall lipophilicity. This study identifies those structural characteristics of Pluronics required for maximal impact on drug efflux transporter activity in bovine brain microvessel endothelial cells (BBMECs). Using a wide range of block copolymers, differing in hydrophilic-lipophilic balance (HLB), this study shows that lipophilic Pluronics with intermediate length of propylene oxide block (from 30 to 60 units) and HLB
-
Pluronic block copolymers in drug delivery from micellar nanocontainers to biological response modifiers
Critical Reviews in Therapeutic Drug Carrier Systems, 2002Co-Authors: Alexander V. Kabanov, Valery AlakhovAbstract:: Pluronic block copolymers are recognized pharmaceutical excipients listed in the US and British Pharmacopoeia. The incorporation of drugs into Pluronic micelles results in increased solubility and stability of drugs. Consequently, the micelles are used for delivery of drugs in the body. Pluronic unimers sensitize multidrug-resistant cells by inhibiting drug efflux transporters. This allows for the development of formulations for the treatment of multidrug-resistant and metastatic tumors. Furthermore, these formulations can be used to enhance brain and oral bioavailability of various drugs. Finally, Pluronic formulations were shown to enhance transgene expression in the body. This opens new possibilities for the use of Pluronic in gene therapies.
K. C. Lowe - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Pluronic F-68 on shoot regeneration from cultured jute cotyledons and on growth of transformed roots
Plant Cell Tissue and Organ Culture, 1993Co-Authors: A. Khatun, Lakhdar Laouar, B J Mulligan, M. R. Davey, J. B. Power, K. C. LoweAbstract:The effects have been studied of the non-ionic surfactant, Pluronic F-68, on the growth in culture of jute ( Corchorus capsularis L.) cotyledons with attached petioles, cotyledon explants and transformed roots. Supplementation of culture medium with 0.001–0.5% (w/v) of either commercial grade Pluronic F-68 or a purified fraction prepared by passage through silica gel, stimulated shoot production from the petioles of C. capsularis var. D154 and C134 cotyledons. This effect was most marked in C134, because of the failure of control cotyledons to produce shoots in the absence of Pluronic. Plants regenerated from Pluronic-treated cotyledons were morphologically normal. Growth of transformed roots of C. capsularis var. D154 was stimulated in medium supplemented with commercial grade or purified Pluronic F-68, with maximum increases in both fresh and dry weights with 0.1% (w/v) of the surfactant. Roots cultured in the presence of Pluronic F-68 could be maintained without sub-culture for up to 70 days, whereas roots cultured in the absence of Pluronic required subculture every 7 days, to prevent necrosis. Transformed roots also produced callus in the presence of 0.001–1.0% (w/v) of either commercial grade or purified Pluronic. The biotechnological implications of these results are discussed in relation to the potential value of non-ionic surfactants as growth-stimulating additives to plant culture media.
-
effects of Pluronic f 68 on callus growth and protoplast plating efficiency of solanum dulcamara
Plant Cell Reports, 1991Co-Authors: V . Kumar, Lakhdar Laouar, B J Mulligan, M. R. Davey, K. C. LoweAbstract:The effects of the non-ionic surfactant, Pluronic F-68, on the growth of callus and protoplasts from Solanum dulcamara L. have been studied. Growth of callus was stimulated by addition of 0.1% (w/v) commercial grade Pluronic to culture medium, whereas lower concentrations (0.01% w/v) had no corresponding effect. In contrast, higher concentrations (1.0% w/v) of Pluronic inhibited callus growth. The mean plating efficiency of protoplasts grown at different densities (15 days after plating) was increased up to 26% following culture with 0.1% (w/v) Pluronic, while 0.01% (w/v) Pluronic was ineffective. Mean protoplast plating efficiency decreased by up to 32% following culture with 1.0% (w/v) Pluronic.
-
effects of Pluronic f 68 on growth of transformed roots of solanum dulcamara
Biotechnology Letters, 1990Co-Authors: V . Kumar, Lakhdar Laouar, B J Mulligan, M. R. Davey, K. C. LoweAbstract:The effects of the non-ionic surfactant, Pluronic F-68, on the growth of transformed roots ofSolanum dulcamara L. have been studied. Growth was stimulated by addition of low concentrations (0.001–0.1% w/v) of freshly-prepared commercial grade Pluronic to liquid culture medium, with maximum increases in root fresh and dry weights at 0.01% (w/v). In contrast, higher concentrations (0.25–1.00% w/v) of freshly-prepared Pluronic inhibited growth. Freshly-prepared purified Pluronic retarded root growth, even at concentrations that were stimulatory with the commercial preparation. Similarly, commercial grade Pluronic solutions stored at 4°C or 22°C for 5 days (“aged”) were inhibitory to root growth.
Tae Gwan Park - One of the best experts on this subject based on the ideXlab platform.
-
thermally reversible Pluronic heparin nanocapsules exhibiting 1000 fold volume transition
Langmuir, 2006Co-Authors: Seung Ho Choi, Sungmin Choi, Tae Gwan ParkAbstract:Novel Pluronic/heparin composite nanocapsules that exhibit a thermally responsible swelling and deswelling behavior were synthesized. Pluronic F-127 preactivated with p-nitrophenyl chloroformate at its two terminal hydroxyl groups was dissolved in a methylene chloride phase. The organic phase was dispersed in an aqueous phase containing heparin. At an organic/aqueous interface, Pluronic-cross-linked heparin nanocapsules were produced. They exhibited a 1000-fold volume transition (ca. 336 nm at 25 °C; ca. 32 nm at 37 °C), and a reversible swelling and deswelling behavior when the temperature was cycled between 20 and 37 °C. The reversible volume transition of Pluronic nanocapsules was caused by micellization and demicellization of cross-linked Pluronic polymer chains within the nanocapsule structure in response to temperature. The morphological characters were investigated with transmission electron microscopy and small angle neutron scattering. Pluronic/heparin nanocapsules had an aqueous fluid-filled hol...
-
Photo-crosslinkable, thermo-sensitive and biodegradable Pluronic hydrogels for sustained release of protein
Journal of Biomaterials Science Polymer Edition, 2004Co-Authors: Jun Bae Lee, Doo Sung Lee, Jun-jin Yoon, Tae Gwan ParkAbstract:Thermo-sensitive and biodegradable hydrogels based on Pluronic tri-block copolymers were prepared by a photo-polymerization method. Two terminal hydroxyl groups in Pluronic F-127 were acrylated to form a Pluronic macromer. Photo-cross-linked Pluronic hydrogels prepared by UV radiation showed a gradually decreased swelling ratio with increasing temperature and exhibited a thermally-responsive change in the swelling ratio when the temperature was cycled between 10degreesC and 37degreesC. These hydrogels degraded slowly due to the cleavage of ester linkage in the acrylated Pluronic terminal end. When lysozyme, a model protein drug, was loaded in the hydrogels, bi-phasic protein release profiles were attained: a burst-free and rapid controlled release profile was initially observed for a one week period and a much slower sustained release was followed thereafter. The release rates could be controlled by varying the amount of Pluronic macromer for photo-polymerization.
-
temperature responsive and degradable hyaluronic acid Pluronic composite hydrogels for controlled release of human growth hormone
Journal of Controlled Release, 2002Co-Authors: Tae Gwan ParkAbstract:Abstract Temperature-sensitive hyaluronic acid (HA) hydrogels were synthesized by photopolymerization of vinyl group modified HA in combination with acrylate group end-capped poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) tri-block copolymer (Pluronic F127). The synthesized HA/Pluronic composite hydrogels gradually collapsed with increasing temperature over the range of 5–40 °C, suggesting that the Pluronic component formed self-associating micelles in the hydrogel structure. Upon prolonged incubation in a buffer medium, the micelles slowly degraded due to the hydrolytic scission of the ester linkage between the Pluronic and acrylate group. The mass erosion occurred much faster at 37 °C than at 13 °C, indicating that at the higher temperature, the ester linkage between the Pluronic and acrylate group might be more exposed to an aqueous environment and thus be more readily hydrolyzed due to Pluronic micellization. Incorporation of recombinant human growth hormone in the hydrogel resulted in a sustained release profile which followed a mass erosion pattern.
K C Sung - One of the best experts on this subject based on the ideXlab platform.
-
in situ gelling of alginate Pluronic solutions for ophthalmic delivery of pilocarpine
Biomacromolecules, 2004Co-Authors: K C Sung, Wenjong VongAbstract:We prepared a series of alginate and Pluronic-based solutions as the in situ gelling vehicles for ophthalmic delivery of pilocarpine. The rheological properties, in vitro release as well as in vivo pharmacological response of polymer solutions, including alginate, Pluronic solution, and alginate/Pluronic solution, were evaluated. The optimum concentration of alginate solution for the in situ gel-forming delivery systems was 2% (w/w) and that for Pluronic solution was 14% (w/w). The mixture of 0.1% alginate and 14% Pluronic solutions showed a significant increase in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 °C. Both in vitro release and in vivo pharmacological studies indicated that the alginate/Pluronic solution retained pilocarpine better than the alginate or Pluronic solutions alone. The results demonstrated that the alginate/Pluronic mixture can be used as an in situ gelling vehicle to increase ocular bioavailability.
-
In situ gelling of alginate/Pluronic solutions for ophthalmic delivery of pilocarpine.
Biomacromolecules, 2004Co-Authors: K C Sung, Wenjong VongAbstract:We prepared a series of alginate and Pluronic-based solutions as the in situ gelling vehicles for ophthalmic delivery of pilocarpine. The rheological properties, in vitro release as well as in vivo pharmacological response of polymer solutions, including alginate, Pluronic solution, and alginate/Pluronic solution, were evaluated. The optimum concentration of alginate solution for the in situ gel-forming delivery systems was 2% (w/w) and that for Pluronic solution was 14% (w/w). The mixture of 0.1% alginate and 14% Pluronic solutions showed a significant increase in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 °C. Both in vitro release and in vivo pharmacological studies indicated that the alginate/Pluronic solution retained pilocarpine better than the alginate or Pluronic solutions alone. The results demonstrated that the alginate/Pluronic mixture can be used as an in situ gelling vehicle to increase ocular bioavailability.
-
carbopol Pluronic phase change solutions for ophthalmic drug delivery
Journal of Controlled Release, 2000Co-Authors: K C SungAbstract:Abstract The major purpose of this study is to develop and characterize a series of carbopol- and Pluronic-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of various polymer solutions, including carbopol, Pluronic and carbopol/Pluronic solution, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel forming delivery systems was 0.3% (w/w), and that for Pluronic solution was 14% (w/w). The mixture of 0.3% carbopol and 14% Pluronic solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25°C. The rheological behaviors of carbopol/Pluronic solution were not affected by the incorporation of pilocarpine hydrochloride. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/Pluronic solution had the better ability to retain drug than the carbopol or Pluronic solutions alone. The results demonstrated that the carbopol/Pluronic mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability.
-
Carbopol/Pluronic phase change solutions for ophthalmic drug delivery
Journal of Controlled Release, 2000Co-Authors: K C SungAbstract:Abstract The major purpose of this study is to develop and characterize a series of carbopol- and Pluronic-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of various polymer solutions, including carbopol, Pluronic and carbopol/Pluronic solution, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel forming delivery systems was 0.3% (w/w), and that for Pluronic solution was 14% (w/w). The mixture of 0.3% carbopol and 14% Pluronic solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25°C. The rheological behaviors of carbopol/Pluronic solution were not affected by the incorporation of pilocarpine hydrochloride. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/Pluronic solution had the better ability to retain drug than the carbopol or Pluronic solutions alone. The results demonstrated that the carbopol/Pluronic mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability.
Magda W Samaha - One of the best experts on this subject based on the ideXlab platform.
-
in sight into tadalafil block copolymer binary solid dispersion mechanistic investigation of dissolution enhancement
International Journal of Pharmaceutics, 2010Co-Authors: Mohammed M Mehanna, Adel M Motawaa, Magda W SamahaAbstract:Abstract Tadalafil is a phosphodiesterase-5 inhibitor that is characterized by low solubility and high permeability. Solid dispersion approach represents a promising carrier system for effective enhancement of dissolution and oral bioavailability of poorly soluble drugs. In the present work, novel tadalafil-loaded solid dispersions employing various block copolymers (Pluronics ® ) were prepared through fusion technique. Their solubility and dissolution properties were compared to the drug alone. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Furthermore, contact angle measurements were carried out. The sign and magnitude of the thermodynamic parameters indicated spontaneity of solubilization process. The phase solubility studies revealed A L type of curves for the carriers. Unlike traditional solid dispersion systems, the crystal form of drug in the formulated systems could not be converted to amorphous form. Most of the studied grades showed dissolution improvement vis-a-vis pure drug, with Pluronic F-127 as the most promising carrier. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model. Thus, the results demonstrated that tadalafil/Pluronic F-127 solid dispersion system is a direct and feasible technology which represents a potential candidate for delivering a poorly water-soluble drug with enhanced solubility and dissolution.
