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Artificial Polymers made of α-amino Acids - Poly(Amino Acid)s, Pseudo-Poly(Amino Acid)s, Poly(Depsipeptide)s, and Pseudo-Proteins.
Zavradashvili, N, Puiggali, J, Katsarava, R
Current pharmaceutical design. 2020;(5):566-593
Abstract
Degradable polymers (DPs) - "green materials" of the future, have an innumerable use in biomedicine, particularly in the fields of tissue engineering and drug delivery. Among these kind of materials naturally occurring polymers - proteins which constituted one of the most important "bricks of life" - α-amino acids (AAs) are highly suitable. A wide biomedical applicability of proteins is due to special properties such as a high affinity with tissues and releasing AAs upon biodegradation that means a nutritive potential for cells. Along with these positive characteristics proteins as biomedical materials they have some shortcomings, such as batch-to-batch variation, risk of disease transmission, and immune rejection. The last limitation is connected with the molecular architecture of proteins. Furthermore, the content of only peptide bonds in protein molecules significantly restricts their material properties. Artificial polymers with the composition of AAs are by far more promising as degradable biomaterials since they are free from the limitations of proteins retaining at the same time their positive features - a high tissue compatibility and nutritive potential. The present review deals with a brief description of different families of AA-based artificial polymers, such as poly(amino acid)s, pseudo-poly(amino acid)s, polydepsipeptides, and pseudo-proteins - relatively new and broad family of artificial AA-based DPs. Most of these polymers have a different macromolecular architecture than proteins and contain various types of chemical links along with NH-CO bonds that substantially expands properties of materials destined for sophisticated biomedical applications.
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An Appraisal on Various Methods of Nano Particulate Formulations.
Dhiman, B, Divtrannum, , Dhiman, A, Saini, S
Pharmaceutical nanotechnology. 2017;(4):255-262
Abstract
BACKGROUND Nanotechnology has immense significance in the field of medicine, agriculture, business, public health sector due to wide applicability of the nano products. Basically, nanotechnology is the incorporation of nanoscale structures into larger material components to improve the properties of constructed system. METHOD Nanotechnology serves as an alternative drug delivery system to the liposomes drug delivery system as the stability of the product in biological fluids is the main problem associated with the liposomal drug delivery system. In the present review, nanoparticles, their applications, various techniques of preparation of nanoparticles and research update on nano particulate drug delivery system have been discussed. RESULTS The main complication associated with biodegradable polymer is uncertainty in their absorption pathway in gastrointestinal tract. Sometimes, harmful by-products after metabolism are released. However, the polymeric nanoparticles (synthetic or semi-synthetic) have a defined structure therefore; get absorbed in intact form in gastrointestinal tract. CONCLUSION Nano-particulate drug delivery system using natural/synthetic polymer may enhance the therapeutic activity of some anti-cancer drug by increasing the host's immune mechanism and antitumor role through improving the body's immune function. It has been observed that despite the technological challenges, nanoparticulate drug delivery system is the most promising drug delivery system in case of anticancer drugs because polymer based nanostructures enhance the bio-adhesiveness and as well as local accumulation of chemotherapeutic agent.
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[Polioxidonium in comprehensive therapy of recurrent herpetic stomatitis in children with allergic diseases].
Kuznetsova, OIu, Maksimovskaia, LN, Balabolkin, II, Gorshenina, AP, Semenov, GV
Stomatologiia. 2008;(6):52-5
Abstract
In the study with participation of 96 children of 1-7 years age with recurrent herpetic stomatitis and allergic diseases therapeutic efficacy of Polioxidonium was investigated. Polioxidonium was used in combination with traditional methods and with He-Ne-laser irradiation. Local oral cavity immunity, indexes of cellular immunity (in the reaction of lymphocytes blast-transformation with phytohemagglutinin), indexes of humoral immunity (IgG and IgE) were studied, complement C(3)-component was determined. Polioxidonium in combination with traditional methods and with laser therapy for recurrent herpetic stomatitis treatment in children with allergic diseases influenced favourably upon clinical course of allergic diseases, let achieve stable remission, increased efficacy of their treatment, promoted immunological status and shorten the terms of medical rehabilitation.
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[Influence of membrane-active polyanions on various stages of the human cytomegalovirus life cycle in vitro].
Pavlova, MV, Fedorova, NE, Serbin, AV, Klimova, EV, Karaseva, EN, Golyshev, SA, Kushch, AA
Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]. 2008;(11-12):3-10
Abstract
Human cytomegalovirus (CMV), an agent of infection (CMVI), lethally dangerous for immune deficient neonates and adults was investigated in vitro as a target for a therapeutic effect of new membrane-active polyanionic compounds (MPC). Previous studies on the alicycle- and sulfate-modified carboxy-MPCs revealed a well-defined tendency of the anti-CMV activity amplification in parallel with increasing of the content of sulfate groups, enhancing the negative charge of the macromolecule. The dominating role of the electrostatic factor was confirmed by the highest activity of AS-688, compound with maximum sulfation among the tested MPCs. Its selectivity index (SI) of the CMVI inhibition in human diploid fibroblast cells reached 5450, 7500, 250 and 4286 in the microbicidal, viricidal, prophylactic and therapeutic schemes of the experiment respectively. The antiviral activity at the first, second and third schemes was explained by the polyanion-typical potential of electrostatic neutralization of the countercharged virions and prevention of the virus adsorption on the cell membranes (in competition with heparin sulfate, a cellular receptor of CMV), whereas the therapeutic effect required the ability of MPC to influence the intracellular stages of the CMV life cycle. The PCR and immunochemical assays revealed an inhibitory action of AS-688 on replication of the viral DNA and the following synthesis of the late viral protein gB with efficiency similar to that of gancyclovir (GCV). However, in contrast to GCV, acting as inhibitor of enzyme (viral RNA-polymerase) factor of the biosynthesis, the therapeutic activity of MPC could be interpreted by competition with viral RNA/DNA due to the specific character of the MPC molecular basis, initially constructed on the principle of nucleic acids backbone and charge adjustable imitation. This mechanism assuming reduction of the cytotoxicity risks, explained the experimentally observed fact of low cytotoxicity of MPCs and possible achievement of high SI. The MPC ability to penetrate into the cells without disruption of cellular membrane permeability was confirmed in experiments with the fluorescent-labeled derivate AS-679, structurally and functionally related to AS-688. In the light of the previously described HIV inhibiting properties of AS-688, AS-679 and MPC analogous, the results could be considered prospective in development of new highly effective agents for combined antiviral protection.
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Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors.
Idzko, M, Dichmann, S, Ferrari, D, Di Virgilio, F, la Sala, A, Girolomoni, G, Panther, E, Norgauer, J
Blood. 2002;(3):925-32
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Abstract
Dendritic cells (DCs) are considered the principal initiators of immune response because of their ability to migrate into peripheral tissues and lymphoid organs, process antigens, and activate naive T cells. There is evidence that extracellular nucleotides regulate certain functions of DCs via G-protein-coupled P2Y receptors (P2YR) and ion-channel-gated P2X receptors (P2XR). Here we investigated the chemotactic activity and analyzed the migration-associated intracellular signaling events such as actin reorganization and Ca(++) transients induced by common P2R agonists such as adenosine 5'-triphosphate (ATP) and 2-methylthioadenosine triphosphate, the P2YR agonists UTP and adenosine 5'-diphosphate (ADP), or the P2XR agonists alphabeta-methylenadenosine-5'-triphosphate and 2',3'-(4-benzoyl)benzoyl-ATP. The common P2R agonists and the selective P2YR agonists turned out to be potent chemotactic stimuli for immature DCs, but not for mature DCs. In contrast, P2XR agonists had only marginal chemotactic activity in both DC types. Chemotaxis was paralleled by a rise in the intracellular Ca(++) concentration and by actin polymerization. Studies with pertussis toxin implicated that intracellular signaling events such as actin polymerization, mobilization of intracellular Ca(++), and migration induced by nucleotides was mediated via G(i/o) protein-coupled P2YR. Moreover, functional studies revealed selective down-regulation of this G(i/o) protein-coupled chemotactic P2YR responsiveness during maturation, although immature and mature DCs expressed similar amounts of mRNA for the P2R subtypes (P2Y(2)R, P2Y(4)R, P2Y(5)R, P2Y(7)R, P2Y(11)R and P2X(1)R, P2X(4)R, P2X(7)R), and no major differences in respect to the mRNA expression of these receptors could be observed by semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). In summary, our data describe a differential chemotactic response of immature and mature DCs to nucleotides, and lend further support to the hypothesis that P2R are a novel class of immunomodulatory plasma membrane receptors suitable for pharmacological intervention.