Proteinoid Nanocapsules As Drug Delivery System for Improving Antipsychotic Activity of Risperidone

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Sep 5

PMID 32887463

Citations 5

Authors

Liroy Lugasi

Igor Grinberg

Rivka Sabag

Ravit Madar

Haim Einat

Shlomo Margel

Affiliations

Soon will be listed here.

Abstract

Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP.

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References

Joseph E, Reddi S, Rinwa V, Balwani G, Saha R . Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects. Eur J Pharm Sci. 2017; 104:315-325. DOI: 10.1016/j.ejps.2017.03.050. View

Sahu R, Verma R, Dixit S, Igietseme J, Black C, Duncan S . Future of human Chlamydia vaccine: potential of self-adjuvanting biodegradable nanoparticles as safe vaccine delivery vehicles. Expert Rev Vaccines. 2018; 17(3):217-227. PMC: 6330895. DOI: 10.1080/14760584.2018.1435279. View

Rukmangathen R, Yallamalli I, Yalavarthi P . Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery. Drug Dev Ind Pharm. 2019; 45(8):1342-1350. DOI: 10.1080/03639045.2019.1619759. View

Sajatovic M, Subramoniam M, Fuller M . Risperidone in the treatment of bipolar mania. Neuropsychiatr Dis Treat. 2009; 2(2):127-38. PMC: 2671778. DOI: 10.2147/nedt.2006.2.2.127. View

George A, Shah P, Shrivastav P . Natural biodegradable polymers based nano-formulations for drug delivery: A review. Int J Pharm. 2019; 561:244-264. DOI: 10.1016/j.ijpharm.2019.03.011. View

Wang K, Huang Q, Qiu F, Sui M . Non-viral Delivery Systems for the Application in p53 Cancer Gene Therapy. Curr Med Chem. 2015; 22(35):4118-36. DOI: 10.2174/0929867322666151001121601. View

Ma X, Santiago N, Chen Y, Chaudhary K, Milstein S, Baughman R . Stability study of drug-loaded proteinoid microsphere formulations during freeze-drying. J Drug Target. 1994; 2(1):9-21. DOI: 10.3109/10611869409015889. View

Marston H, Young J, Martin F, Serpa K, Moore C, Wong E . Asenapine effects in animal models of psychosis and cognitive function. Psychopharmacology (Berl). 2009; 206(4):699-714. PMC: 2755103. DOI: 10.1007/s00213-009-1570-z. View

Mokhtarzadeh A, Alibakhshi A, Yaghoobi H, Hashemi M, Hejazi M, Ramezani M . Recent advances on biocompatible and biodegradable nanoparticles as gene carriers. Expert Opin Biol Ther. 2016; 16(6):771-85. DOI: 10.1517/14712598.2016.1169269. View

10.

Mannhold R . The impact of lipophilicity in drug research: a case report on beta-blockers. Mini Rev Med Chem. 2005; 5(2):197-205. DOI: 10.2174/1389557053402701. View

11.

Araseki M, Yamamoto K, Miyashita K . Oxidative stability of polyunsaturated fatty acid in phosphatidylcholine liposomes. Biosci Biotechnol Biochem. 2003; 66(12):2573-7. DOI: 10.1271/bbb.66.2573. View

12.

Riley R, Parker A, Trigg S, Manners C . Development of a generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery. Pharm Res. 2001; 18(5):652-5. DOI: 10.1023/a:1011085411050. View

13.

Jamshidian M, Tehrany E, Imran M, Jacquot M, Desobry S . Poly-Lactic Acid: Production, Applications, Nanocomposites, and Release Studies. Compr Rev Food Sci Food Saf. 2021; 9(5):552-571. DOI: 10.1111/j.1541-4337.2010.00126.x. View

14.

Sun F, Su Z, Sui C, Zhang C, Yuan L, Meng Q . Studies on the acute toxicity, pharmacokinetics and pharmacodynamics of paliperidone derivatives--comparison to paliperidone and risperidone in mice and rats. Basic Clin Pharmacol Toxicol. 2010; 107(2):656-62. DOI: 10.1111/j.1742-7843.2010.00552.x. View

15.

Das S, Ng W, Kanaujia P, Kim S, Tan R . Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables. Colloids Surf B Biointerfaces. 2011; 88(1):483-9. DOI: 10.1016/j.colsurfb.2011.07.036. View

16.

Pellow S, Chopin P, File S, Briley M . Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985; 14(3):149-67. DOI: 10.1016/0165-0270(85)90031-7. View

17.

Quirk S . Triggered release of small molecules from proteinoid microspheres. J Biomed Mater Res A. 2008; 91(2):391-9. DOI: 10.1002/jbm.a.32241. View

18.

Megens A, Awouters F, SCHOTTE A, Meert T, Dugovic C, NIEMEGEERS C . Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994; 114(1):9-23. DOI: 10.1007/BF02245439. View

19.

Cryan J, Holmes A . The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov. 2005; 4(9):775-90. DOI: 10.1038/nrd1825. View

20.

Calzoni E, Cesaretti A, Polchi A, Di Michele A, Tancini B, Emiliani C . Biocompatible Polymer Nanoparticles for Drug Delivery Applications in Cancer and Neurodegenerative Disorder Therapies. J Funct Biomater. 2019; 10(1). PMC: 6463038. DOI: 10.3390/jfb10010004. View