Short Communication - Journal of Pharmaceutical Chemistry & Chemical Science (2022) Volume 6, Issue 2
In A549 lung cells, pair formation and uptake via the polyamine transporter.
School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore, Madhya Pradesh, India
- *Corresponding Author:
- Vishaka Nagole
School of Pharmacy
Devi Ahilya Vishwavidyalaya, Indore
Madhya Pradesh, India
Received: 02-Apr-2022, Manuscript No. AAPCCS-22-64082; Editor assigned: 04-Apr-2022, PreQC No. AAPCCS-22-64082(PQ); Reviewed: 18-Apr-2022, QC No. AAPCCS-22-64082; Revised: 22-Apr-2022, Manuscript No. AAPCCS-22-64082(R); Published: 29-Apr-2022, DOI:10.35841/aapccs-6.2.110
Citation: Nagole V. In A549 lung cells, pair formation and uptake via the polyamine transporter. J Pharm Chem Chem Sci. 2022;6(2):110
All cells contain the natural ketones are organic compounds putrescine, cadaverine, spermidine, and spermine. Anions, such as DNA and RNA, interact with these (poly) cations. This characteristic represents their most well-known direct physiological role in cellular functions: cell division, proliferation, and differentiation. The lungs, and specifically alveolar epithelial cells, appear to have a considerably more powerful polyamine absorption system than any other major organ. The active buildup of natural polyamines in the epithelium of the rat, hamster, rabbit, and human lungs has been examined in numerous mammalian species. Regardless of the polyamine or species analysed or the in vitro system employed, the uptake system's kinetic characteristics (MichaelisMenten constant and maximal uptake) are of the same order of magnitude. Polyamines are also accumulated by other pulmonary cells, but not to the same level as the epithelium. Although the lungs have separate uptake mechanisms for putrescine, spermidine, and spermine, neither the nature nor the cause for their existence is known.
After administration, medicines linked to targeting ligands can achieve preferential accumulation of therapeutic molecules in target tissues. This method can assist keep drugs at their intended place of action by reducing off-target negative effects. Polyamine biosynthesis and/or polyamine concentration in the lungs have been linked to a variety of pulmonary toxicological and pathological disorders . The inherent toxicity of polyamines is quite high. Spermidine and spermine can be converted to h2o2, ammonium, and acrolein in nonpulmonary cells, according to in vitro research. Increased polyamine production and polyamine concentration in the rat lung are linked to animal survival in hyperoxia or after ozone exposure. Increased polyamine metabolism and lung polyamine concentration have been associated to pulmonary hypertension caused by monocrotaline or hypoxia. Polyamines have been found to help inhibit immunological reactions in the lungs in a modest number of trials .
However, linking targeted ligands to many low - molecular - weight actives in a way that does not affect their pharmacological action remains a challenge. Polyamine targeting ligands, for example, are extremely effective at targeting small molecular weight anticancer treatments to tumours, but their covalent connection to the targeted drugs changes their overall characteristics, reducing their anticancer efficacy . Similarly, putting small molecular weight pharmaceuticals onto ligand-decorated carriers can preserve the molecule and promote its cellular absorption, but the carrier release process can slow down drug action. As a result, many targeted tactics are inadequate for the treatment of acute illnesses, such as medical crises, where tailored drug delivery systems are lacking .
The dissociation rate of an ion-paired system can be controlled by the complex connection strength, which is a benefit of attaching the targeted ligand to the drug by ion-pair formation. As a result, using ion-pairs with moderate association strength eliminates any negative impact on medication pharmacological action. However, because of the quick dissociation kinetics of the theophylline-spermine ion-pair, the effects produced utilising an ion-paired polyamine targeting ligand were short-lived, implying that more research is needed to understand ion-pair half-life in vivo .
The results of this study showed that spermine-tagged theophylline-CD supramolecular assemblages optimised for PTS absorption can target theophylline distribution to the lungs. Because CD increased the ion-pair half-life, it was an important component of the assemblies for in vivo enhancement. The use of ion-pairing to bind the targeted ligand to the drug was a valuable method since it allowed easy drug release at the site of action. When the systemic dose of theophylline is limited by a small therapeutic window, selective targeting to produce a quick 2-fold increase in lung delivery may be a viable option.
- Mitchell JLA, Judd GG, Bareyal-Leyser A. Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells. Biochem J. 1994;299(1):19-22.
- Larsson LI, Morchjorgensen L, Hougaard DM. Cellular and sub-cellular localization of polyamines cytochemical methods providing new clues to polyamine function in normal and neoplasticcells. Histochem. 1982;76:159-174.
- Goyns MH. Changes in the nuclear polyamine content of chick erythrocytes during embryonic development. Biochem J. 1979;184(3): 607-612.
- Swanson JA, Yirinec BD, Silverstein SC. Phorbol esters and horseradish-peroxidase stimulate pinocytosis and redirect the flow of pinocytosed fluid in macrophages. J Cell Biol. 1985;100:851-859.
- Altenberg GA, Vanoye CG, Horton JK et al. Unidirectional fluxes of rhodamine 123 in multidrug resistant cells: evidence against direct extrusion from the plasma membrane. Proc Natl Acad Sci USA. 1994;91(11):4654-4657.