Quantum Dot loaded BQCA‐Octadecylamine conjugate nanosystems for theranostic applications in Alzheimer’s Disease.

Abstract

AbstractBackgroundAlzheimer’s Disease (AD) is one of the most common types of dementias in the world and is characterized by progressive, irreversible neurodegeneration. Benzyl quinolone carboxylic acid was shown to have beneficial in management of AD. The current challenge with BQCA is its low brain half‐life, permeability and rapid elimination. The above challenge can be answered by formulating lipid drug conjugates of BQCA, with octadecyl amine (BQCA‐ODA). Quantum dots (QDs) with their unique optical properties, with high sensitivity and stability emerging as theranostic agents in several neurodegenerative diseases. Hypothesizing the co‐delivery of QDs and BQCA for the effective treatment of AD, in the present study we have formulated lipid nano carriers loaded with quantum dots (QDs) surface modified with Polysorbate 80, called PS80‐QD‐BQCA‐ODA‐NPs, for integrating imaging and therapy for effective management of AD.MethodBQCA was conjugated to Octadecyl amine (ODA), to form BQCA‐ODA LDC conjugate. The amphiphilic nature of the BQCA‐ODA conjugate allows the formation of self‐assembled nanoparticles. Here, we have employed solvent injection method followed by sonication, while addition of QDs in the organic phase and P80 in the aqueous phase to form PS80‐QD‐BQCA‐ODA‐NPs . The optimized formulation was evaluated for physicochemical properties (particle size, zeta potential and polydispersity index) surface morphology and in vitro drug release. The in vitro biocompatibility of the PS80‐QD‐BQCA‐ODA‐NPs was assessed on RBC and SHSY‐5Y cell lines. Further the application of PS80‐QD‐BQCA‐ODA‐NPs was assessed by in vivo imaging and behavioural studies on STZ induced mice models of AD.ResultThe formation of BQCA‐ODA conjugate formation was confirmed 13C‐NMR, 1H‐NMR, LC‐MS. The optimized PS80‐QD‐BQCA‐ODA‐NPs were found to have a near spherical shape with a particle size (PS) of 152.62 ± 1.82 nm, zeta potential (ZP) of 18.59 ± 0.56 mV and polydispersity index (PDI) of 0.214±0.08. PS80‐QD‐BQCA‐ODA‐NPs. The NPs shown improved brain permeability, with greater fluorescence intensity in mouse brains when compared to free QDs. In the in vivo efficiency studies PS80‐QD‐BQCA‐ODA‐NPs shown a significant improvement in memory in mice models.ConclusionThe PS80‐QD‐BQCA‐ODA‐NPs nanomedicine was successfully prepared, thoroughly characterized and has shown theronostic benefits in AD mice models.