| pubmed-article:21514661 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21514661 | lifeskim:mentions | umls-concept:C0085104 | lld:lifeskim |
| pubmed-article:21514661 | lifeskim:mentions | umls-concept:C0030956 | lld:lifeskim |
| pubmed-article:21514661 | lifeskim:mentions | umls-concept:C2698650 | lld:lifeskim |
| pubmed-article:21514661 | lifeskim:mentions | umls-concept:C0596383 | lld:lifeskim |
| pubmed-article:21514661 | lifeskim:mentions | umls-concept:C0908536 | lld:lifeskim |
| pubmed-article:21514661 | pubmed:issue | 22 | lld:pubmed |
| pubmed-article:21514661 | pubmed:dateCreated | 2011-5-23 | lld:pubmed |
| pubmed-article:21514661 | pubmed:abstractText | Membranolytic macromolecules are promising vehicles for cytoplasmic drug delivery, but their efficiency and safety remains primary concerns. To address those concerns, membranolytic properties of various poly(?-L-malic acid) (PMLA) copolymers were extensively investigated as a function of concentration and pH. PMLA, a naturally occurring biodegradable polymer, acquires membranolytic activities after substitution of pendent carboxylates with hydrophobic amino acid derivatives. Ruled by hydrophobization and charge neutralization, membranolysis of PMLA copolymers increased as a function of polymer molecular weight and demonstrated a maximum with 50% substitution of carboxylates. Charge neutralization was achieved either conditionally by pH-dependent protonation or permanently by masking carboxylates. Membranolysis of PMLA copolymers containing tripeptides of leucine, tryptophan and phenylalanine were pH-dependent in contrast to pH-independent copolymers of Leucine ethyl ester and Leu-Leu-Leu-NH(2) with permanent charge neutralization. PMLA and tripeptides seemed a unique combination for pH-dependent membranolysis. In contrast to nontoxic pH-dependent PMLA copolymers, pH-independent copolymers were found toxic at high concentration, which is ascribed to their nonspecific disruption of plasma membrane at physiological pH. pH-Dependent copolymers were membranolytically active only at acidic pH typical of maturating endosomes, and are thus devoid of cytotoxicity. The PMLA tripeptide copolymers are useful for safe and efficient cytoplasmic delivery routed through endosome. | lld:pubmed |
| pubmed-article:21514661 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21514661 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21514661 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21514661 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21514661 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:21514661 | pubmed:issn | 1878-5905 | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:BlackKeith... | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:HollerEggehar... | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:GIPSC DCD | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:LjubimovaJuli... | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:PatilRameshwa... | lld:pubmed |
| pubmed-article:21514661 | pubmed:author | pubmed-author:Portilla-Aria... | lld:pubmed |
| pubmed-article:21514661 | pubmed:copyrightInfo | Copyright © 2011 Elsevier Ltd. All rights reserved. | lld:pubmed |
| pubmed-article:21514661 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21514661 | pubmed:volume | 32 | lld:pubmed |
| pubmed-article:21514661 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21514661 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21514661 | pubmed:pagination | 5269-78 | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:meshHeading | pubmed-meshheading:21514661... | lld:pubmed |
| pubmed-article:21514661 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21514661 | pubmed:articleTitle | The optimization of polymalic acid peptide copolymers for endosomolytic drug delivery. | lld:pubmed |
| pubmed-article:21514661 | pubmed:affiliation | Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd, Davis 2094A, Los Angeles, CA 90048, USA. Hui.Ding@cshs.org | lld:pubmed |
| pubmed-article:21514661 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21514661 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21514661 | pubmed:publicationType | Evaluation Studies | lld:pubmed |
| pubmed-article:21514661 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
