In VitroEvaluation of Curcumin-Encapsulated Chitosan Nanoparticles against Feline Infectious Peritonitis Virus and Pharmacokinetics Study in Cats

Abstract

Feline infectious peritonitis (FIP) is an important feline viral disease, causing an overridden inflammatory response that results in a high mortality rate, primarily in young cats. Curcumin is notable for its biological activities against various viral diseases; however, its poor bioavailability has hindered its potential in therapeutic application. In this study, curcumin was encapsulated in chitosan nanoparticles to improve its bioavailability. Curcumin-encapsulated chitosan (Cur-CS) nanoparticles were synthesised based on the ionic gelation technique and were spherical and cuboidal in shape, with an average particle size of 330 nm and +42 mV in zeta potential. The nanoparticles exerted lower toxicity in Crandell-Rees feline kidney (CrFK) cells and enhanced antiviral activities with a selective index (SI) value three times higher than that of curcumin. Feline-specific bead-based multiplex immunoassay and qPCR were used to examine their modulatory effects on proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin- (IL-) 6, and IL-1β. There were significant decrements in IL-1β, IL-6, and TNFα expression in both curcumin and Cur-CS nanoparticles. Based on the multiplex immunoassay, curcumin and the Cur-CS nanoparticles could lower the immune-related proteins in FIP virus (FIPV) infection. The single- and multiple-dose pharmacokinetics profiles of curcumin and the Cur-CS nanoparticles were determined by high-performance liquid chromatography (HPLC). Oral delivery of the Cur-CS nanoparticles to cats showed enhanced bioavailability with a maximum plasma concentration (Cmax) value of 621.5 ng/mL. Incorporating chitosan nanoparticles to deliver curcumin improved the oral bioavailability and antiviral effects of curcumin against FIPV infection. This study provides evidence for the potential of Cur-CS nanoparticles as a supplementary treatment of FIP.

Recent Advances on Nanomaterials to COVID‐19 Management: A Systematic Review on Antiviral/Virucidal Agents and Mechanisms of SARS‐CoV‐2 Inhibition/Inactivation

“…Of the 46 research papers retrieved for qualitative synthesis, several investigated nanomaterials potential against animal models and cell lines of 3 genera of Coronaviridae family causative illness in animals (n = 6) and humans (n = 6), including alpha-coronavirus (n = 6), beta-coronavirus (n = 5), and gammacoronavirus (n = 1). Related to 6 types of coronavirus originated in animals, were found 12 articles reporting nanomaterials against transmissible gastroenteritis virus (TGEV), [58] avian infectious bronchitis virus (IBV), [59] feline coronavirus (FCoV), [60] murine hepatitis virus (MHV), [61] type II feline infectious peritonitis virus (FIPV), [62,63] and porcine epidemic diarrhea virus (PEDV). [64][65][66][67][68][69] Concerning the 6 types of coronavirus cause illnesses in people were found 33 different studies reporting the role of nanomaterials against human coronavirus NL63 (HCoV NL63), human coronavirus OC43 (HCoV OC43), [61,70] human coronavirus 229E modified containing a renilla luciferase reporter gene (HCoV-229E-Luc), [71] human MERS-CoV, [72,73] human SARS-CoV, [74] and novel human SARS-CoV-2.…”

“…[45] We collected data from several nanostructures' types studied against the coronavirus cited above as nanotubes, nanorods, nanoparticles, nanostars, nanowires, nanocrystals, nanosheets, nanogels, nanospheres, nanocapsules, nanoclusters, and nanostructured lipid carriers (NLCs). Of these, were identified the following nanotechnology-based approaches: bioconjugated carboxyl quantum dots (QDs); [74] silver nanomaterials; [58,60,69,80,96,97] synthetic virus-like particles (sVLPs); [77] gold nanoparticles; [59,77] biopolymeric/biodegradable polymeric nanoparticles and hydrogels (e.g., chitosan, collagen, poly(ethylene glycol) (PEG), poly lactic-co-glycolic acid (PLGA), and poly(hydroxyethyl) methacrylate); [61,62,63,79,[85][86][87]91,93] carbon quantum dots (CQDs) [71] and cationic carbon dots based on curcumin (CCM-CDs); [68] glutathione(GSH)-capped silver-sulfide nanoclusters (GSHcapped Ag 2 S NCs); [64] gold nanorod-based heptad repeat 1 (HR1) peptide; [72] antigen and adjuvant-loaded hollow polymeric nanoparticles; [73] bovine serum albumin (BSA)-coated tellurium nanoparticles (Te/BSA NPs) with a unique triangular star shape (Te/BSA nanostars); [65] GSH-modified zinc-sulfide nanoparticles (ZnS NPs); [66] glycyrrhizic-acid-based carbon dots (Gly-CDs); [67] multi-walled carbon nanotubes (MWCNTs) with target functions; [83] metal-decorated single-wall carbon nanotubes (SWCNTs); [100] NLCs; [88] graphene oxide; [60,82,92] iron oxide nanoparticles (IONPs), [75] functionalized graphene sheets;…”

“…From Table 6, we note that most of all nanoparticles studied are spherical and presented an impressive average size varying from 11.4 to 1.5 nm in the last 3 years reported atte mpts. [63,64,[66][67][68]91,93] Figure 6 shows a schematic representation of some strategies reviewed on active phytochemicals (a broad-spectrum "host-targeted" antiviral)/nanoparticles systems as promising candidates against coronaviruses as virus adsorbents, antiviral agents. and immunomodulatory drugs.…”

“…Once the low bioavailability impairs its therapeutic application, curcumin was encapsulated in chitosan nanoparticles by ionic gelation technique with improved in vitro antiviral activity and bioavailability by oral administration in cats infected with FIPV. [63] PolyP, a non-toxic and non-immunogenic inorganic polymer derived from marine bacteria, was added into a mucin/collagenbased hydrogel to simulate the mucus of the nasopharynx and bronchial epithelium on human alveolar basal epithelial A549 cells. [91] This strategy was suggested to stimulate an innate antiviral response by improved mucin barrier (high in antimicrobial proteins) and as a potential antiviral agent by exerting protection against SARS-CoV-2-cell attachment.…”

Nanotherapeutics for treating coronavirus diseases

“…In addition, the therapeutic efficiencies of different antiviral agents and immunomodulatory medicines against FIPV have been studied in previous studies, but most were to avail. Nevertheless, recent studies have shown that itraconazole, a common antifungal drug, GC376 3C-like protease inhibitor, and nucleoside analogue GS-441524, are effective in inhibiting infection in cats with naturally occurring FIP [ 129 ].…”