Pinocytic capture and exocytosis of rat immunoglobulin IgG-N-(2-hydroxy-propyl)methacrylamide copolymer conjugates by rat visceral yolk sacs cultured in vitro

1986 ◽  
Vol 6 (10) ◽  
pp. 869-877 ◽  
Author(s):  
Ruth Duncan ◽  
Hazel C. Cable ◽  
Jiri Strohalm ◽  
Jindřich Kopeček
Keyword(s):  
Drug Carrier ◽  
Yolk Sac ◽  
Membrane Receptors ◽  
Cellular Transport ◽  
Hpma Copolymer ◽  
Intracellular Degradation ◽  
Hpma Copolymers ◽  
Hydroxypropyl Methacrylamide ◽  
Covalently Bound

Rat immunoglobulin (IgG) was covalently bound to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers via glycylglycyl spacer. The resultant conjugate, free IgG and HPMA copolymer (containing a low percentage of tyrosinamide to facilitate radiolabelling) were radioiodinated, and their rates of pinocytic uptake, intracellular degradation and exocytic release by rat visceral yolk sacs cultured in vitro were determined. Free IgG was pinocytosed rapidly by the yolk sac and some IgG was subject to intracellular proteolysis. In comparison the IgG-HPMA copolymer conjugate was captured more slowly, but faster than unmodified HPMA. IgG was also exocytosed rapidly by the yolk sac following pinocytic capture and similarly IgG-HPMA copolymer had a much higher rate of release than unmodified H PMA. Measurement of tissue accumulation of125I-labelled IgG-H PMA copolymer in the presence of increasing concentrations of non-radiolabelled IgG showed competition for membrane binding sites between the free, and polymer-bound immunoglobulin. These experiments indicate that immunoglobulins can be covalently bound to a soluble polymer developed as a drug-carrier in such a way that they can still interact with specific membrane receptors and they are subsequently subjected to specific cellular transport mechanisms.

scholarly journals Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1242
Author(s):  
Júlia Kudláčová ◽  
Lenka Kotrchová ◽  
Libor Kostka ◽  
Eva Randárová ◽  
Marcela Filipová ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Drug Carrier ◽  
In Vitro Models ◽  
Hpma Copolymer ◽  
Polymer Carriers ◽  
Hydroxypropyl Methacrylamide ◽  
Tumor Accumulation ◽  
Structural Architecture ◽  
Relationship Of

Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system.

Synthesis and Photoproperties of a Substituted Zinc(II) Phthalocyanine-N-(2-hydroxypropyl)methacrylamide Copolymer Conjugate

1993 ◽  
Vol 58 (10) ◽  
pp. 2321-2336 ◽  
Author(s):  
Zhong-wei Gu ◽  
John D. Spikes ◽  
Pavla Kopečková ◽  
Jindřich Kopeček
Keyword(s):  
Organic Solvents ◽  
Water Soluble ◽  
Lower Probability ◽  
Hpma Copolymer ◽  
Polymeric Derivative ◽  
Oxygen Generation ◽  
Hpma Copolymers ◽  
Hydroxypropyl Methacrylamide ◽  
Polymeric Carriers ◽  
Thiol Proteinases

In cancer photodynamic therapy (PDT), improved efficiency of photosensitizer delivery to tumors may be obtained by binding them to targetable water soluble polymeric carriers. However, attachment of photosensitizers to Macromolecular carriers may alter their spectral and photosensitizing properties. In this study, a new monosubstituted phthalocyanine derivative, N-glycyl zinc(II) 4,9,16,23-tetraaminophthalocyanine (G-TAPC-Zn) was synthesized by the reaction of zinc(II) 4,9,16,23-tetraaminophthalocyanine (TAPC-Zn) with N-tert-butoxycarbonyl-glycine N'-hydroxybenzotriazole ester followed by deprotection of the tert-butoxycarbonyl (BOC) group. G-TAPC-Zn contains an aliphatic amino group suitable for attachment to water soluble polymeric carriers. By aminolysis of a polymeric precursor, an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer containing oligopeptide (GFLG) side-chains terminated in p-nitrophenyl ester groups, with G-TAPC-Zn a polymeric derivative of the latter (P-GFLGG-TAPC-Zn) was synthesized. Spectral data indicated that in aqueous solutions P-GFLGG-TAPC-Zn formed aggregates. The degree of aggregation decreased with increasing concentration of detergents or organic solvents in buffer solutions. Consequently, the release of the drug from carrier catalyzed by thiol proteinases, papain or cathepsin B, took place only in the presence of detergents or organic solvents, i.e., under conditions with a lower probability of aggregate formation. Binding of G-TAPC-Zn to HPMA copolymers decreased the quantum yield of singlet oxygen generation from 0.24 to 0.063 and significantly increased its resistance to photobleaching.

scholarly journals Synthesis of Water-Soluble Star Polymers Based on Cyclodextrins

2018 ◽  
pp. S357-S365
Author(s):  
L. KOTRCHOVÁ ◽  
T. ETRYCH
Keyword(s):  
Star Polymers ◽  
Water Soluble ◽  
Hpma Copolymer ◽  
Polymer Carriers ◽  
Physico Chemical ◽  
Reversible Addition ◽  
Degradation Rates ◽  
Hpma Copolymers ◽  
Hydroxypropyl Methacrylamide ◽  
Chain Transfer Polymerization

Novel star polymers based on the water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer and cyclodextrin were synthesized and the physico-chemical behavior of these precursors was studied. Semitelechelic HPMA copolymers were grafted onto the cyclodextrin core, thus forming star-like structure. Both prepared systems were designed as possible polymer carriers for the controlled release of cytostatic drugs, which after the drug release and degradation will be eliminated from the organism. Two synthesis approaches were used to obtain similar polymer carriers with different degradation rates. All the polymers were prepared by reversible addition-fragmentation chain-transfer polymerization, which guarantees low dispersity of the prepared systems.

scholarly journals Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro.

1975 ◽  
Vol 64 (1) ◽  
pp. 123-134 ◽  
Author(s):  
K E Williams ◽  
E M Kidston ◽  
F Beck ◽  
J B Lloyd
Keyword(s):  
Plasma Membrane ◽  
Initial Period ◽  
Yolk Sac ◽  
Membrane Receptors ◽  
Protein Uptake ◽  
Quantitative Studies ◽  
Intracellular Digestion ◽  
Visceral Yolk Sac ◽  
Plasma Membrane Receptors

Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.

A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben
Keyword(s):  
Systematic Review ◽  
Antioxidant Activity ◽  
Membrane Receptors ◽  
Cancer Development ◽  
Secretory Product ◽  
Prevention And Treatment ◽  
G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

2018 ◽  
Vol 18 (2) ◽  
pp. 302-311
Author(s):  
Shulin Dai ◽  
Yucheng Feng ◽  
Shuyi Li ◽  
Yuxiao Chen ◽  
Meiqing Liu ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Drug Carrier ◽  
Drug Loading ◽  
Drug Carriers ◽  
Cancer Drug ◽  
Drug Release Profile ◽  
Sustained Drug Release ◽  
Anti Cancer ◽  
Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Semi-Crystalline Copolymer Hydrogels as Smart Drug Carriers: In Vitro Thermo-Responsive Naproxen Release Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 158
Author(s):  
Snežana Ilić-Stojanović ◽  
Ljubiša Nikolić ◽  
Vesna Nikolić ◽  
Slobodan Petrović ◽  
Violeta Oro ◽  
...  
Keyword(s):  
Drug Carrier ◽  
Drug Carriers ◽  
Xrd Analysis ◽  
Hplc Method ◽  
Potential Candidate ◽  
Swelling Kinetic ◽  
Model Drug ◽  
Xrd Techniques ◽  
Responsive Hydrogels

In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of application as a thermo-responsive carrier for prolonged naproxen release in order to evaluate as a potential candidate for drug carrier in future pharmaceutical applications.

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