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

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.

Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

“…As expected, all drug-bearing NCs exhibited significantly larger hydrodynamic diameters (see Table 1 ). Following indirect PEGylation, the hydrodynamic diameter with Dox and TRAIL increased to 130 ± 17 nm and 146 ± 16 nm from 118 ± 7 nm and 134 ± 32 nm, respectively, as shown in Figure 2 F. Zeta potential (ζ-potential) measurement at physiological pH (7.4) demonstrated a significant negative charge for the hollow and non-PEGylated drug-bearing P(RGD) NCs due to the carboxyl residue on the particle surface [ 36 , 37 , 47 ]. As observed recently [ 36 ], the elevated ζ-potential of the PEGylated NCs may indicate a successful conjugation of PEG to the surface residues of the P(RGD) NCs.…”

Tumor-Targeted Fluorescent Proteinoid Nanocapsules Encapsulating Synergistic Drugs for Personalized Cancer Therapy

“…The hollow and 25% drug-loaded NCs demonstrated a hydrodynamic diameter of 34 ± 5 and 22 ± 3 nm, respectively, as shown in Figure 4 and Table 2. The dry diameter (HR-SEM) is commonly much lower than the hydrodynamic diameter due to hydrated water layers adsorbed onto the particle surface, in addition to water molecules entrapped within the particles [25,28], e.g., iron oxide nanoparticles prepared in our laboratory possessed average dry and hydrodynamic diameters of 18 and 70 nm, respectively [51]. Similarly, bisphosphonate nanoparticles had average dry and hydrodynamic diameters of 43 and In conclusion, we decided to continue with 25% mixed drugs/NCs (50% yielded only a slightly higher DL, see Table 2).…”

“…Suitable molecules can be encapsulated within the internal core of the formed particle owing to hydrophobic residues; a marker (e.g., a fluorescent label) can be conjugated to the surface using hydrophilic residues such as amines [ 20 ]. Previous studies presented the encapsulation of various molecules for cosmetics (retinoic acid [ 21 ]), chemotherapeutics (doxorubicin and Paclitaxel [ 18 , 22 , 23 ], cannabidiol [ 24 ]), antipsychotics (Risperidone [ 25 ]) and dyes for diagnostic imaging (ICG [ 26 , 27 ]).…”

“…Suitable molecules can be encapsulated within the internal core of the formed particle owing to hydrophobic residues; a marker (e.g., a fluorescent label) can be conjugated to the surface using hydrophilic residues such as amines [20]. Previous studies presented the encapsulation of various molecules for cosmetics (retinoic acid [21]), chemotherapeutics (doxorubicin and Paclitaxel [18,22,23], cannabidiol [24]), antipsychotics (Risperidone [25]) and dyes for diagnostic imaging (ICG [26,27]). D-arginine (R), glycine (G) and L-aspartic acid (D) were used for randomly achieving the RGD sequence within the proteinoid backbone; previous studies showed that 13% of the established proteinoids contain the RGD sequence [26,28].…”

Evaluating Non-Conventional Chitosan Sources for Controlled Release of Risperidone

“…Therefore, its formulation is critical for an appropriate drug release pattern. Different risperidone formulations for extended-release have been described, for instance, RSP has been formulated in polymeric PEG-PGLA microparticles has [ 15 ], in fast dilution tablets [ 16 ], in pegylated proteinoid nanocapsules [ 16 ], in PLGA-microplates [ 17 ] or orodispersible films [ 18 ]. Chitosan has been used in the formulation of RSP drug delivery system in the form of nanoparticles [ 19 ] and mucoadhesive nanoemulsions [ 20 ].…”