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. 2020 Sep 2;25(17):4013.
doi: 10.3390/molecules25174013.

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

Liroy Lugasi  1 , Igor Grinberg  1 , Rivka Sabag  2 , Ravit Madar  3 , Haim Einat  4 , Shlomo Margel  1
Affiliations

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

Liroy Lugasi et al. Molecules. .

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.

Keywords: drug delivery; nanocapsules; proteinoid nanoparticles; risperidone; self-assembly.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of risperidone.
Figure 2
Figure 2
Proton (A) and carbon (B) NMR spectra of as-obtained P(EFH-PLLA) proteinoid.
Figure 3
Figure 3
Hydrodynamic size histograms obtained by dynamic light scattering and cryogenic transmission electron microscope images of P(EFH-PLLA) (A,B) and P(EFH-PLLA)/RSP (C,D).
Figure 4
Figure 4
XTT cell viability assay on murine J774A.1 and Neuro-2α cells after 48 h.
Figure 5
Figure 5
Release of risperidone (RSP) from PEGylated P(EFH-PLLA)/RSP nanoparticles (NPs) in a phosphate buffered saline (PBS) and human serum at 37 °C over a 24 h period. Each data point represents the mean of three samples.
Figure 6
Figure 6
Biodistribution of P(EFH-PLLA) NPs. One hundred µL of Cy7-conjugated NPs (0.2 mg/mL) were injected IV via the tail vein. Mice were sacrificed 4 h post injection, and organs were harvested.
Figure 7
Figure 7
Distance analysis using ANOVA (analysis of variance) of open field test with hollow and RSP-loaded NP treatment 0–30 min prior to amphetamine administration and 30–60 min post amphetamine uptake. Asterisks (*) denote statistical significance versus saline and the hashtag (#) signifies the effect of amphetamine administration.
Figure 8
Figure 8
Mean speed analysis using ANOVA of open field test with hollow and drug-loaded NPs treated 0–30 min prior to amphetamine administration and 30–60 min post amphetamine uptake. Asterisks (*) denote statistical significance versus saline and the hashtag (#) signifies the effect of amphetamine administration.
Figure 9
Figure 9
Center time analysis using ANOVA of open field test with hollow and drug-loaded NP treatment 0–30 min prior to amphetamine administration and 30–60 post amphetamine uptake. Asterisks (*) denote statistical significance versus saline and the hashtag (#) signifies the effect of amphetamine administration.
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