Tetrahydrocurcumin nanolipid carrier system for intranasal administration to the brain

Abstract

A system for the production of tetrahydrocurcumin-loaded nanolipid carriers, consisting of modules for melting, emulsifying, homogenizing and cooling lipids, configured to produce nanoparticles with controlled size and high encapsulation efficiency.

Description

Field of invention

[0001] The invention relates to a nanolipid carrier system for the intranasal administration of tetrahydrocurcumin with the aim of improving targeting accuracy in the brain, stability, bioavailability and therapeutic efficacy against amyloid deposits. Background of the invention

[0002] Tetrahydrocurcumin (THC) is a potent polyphenolic compound with strong anti-amyloid, antioxidant, and neuroprotective properties. However, its therapeutic use is severely limited due to its low water solubility, rapid degradation at physiological pH, and low systemic bioavailability. Furthermore, the blood-brain barrier hinders its entry into the central nervous system, thus reducing its efficacy in treating neurodegenerative diseases such as Alzheimer's and Parkinson's. Conventional delivery systems do not ensure sufficient drug stability or achieve adequate concentrations in the brain. Nanolipid carriers (NLCs), consisting of solid and liquid lipid matrices, have proven to be promising systems for improving solubility, encapsulation efficiency, and delayed drug release.However, developing an optimized NLC system requires careful control of formulation variables to achieve the desired particle size, stability, and release profile. Furthermore, non-invasive routes of administration, such as intranasal delivery, allow direct access to the brain and bypass systemic barriers. Therefore, there is a need for a safe, optimized NLC system that enables efficient intranasal delivery and controlled release of THC. Summary of the invention

[0003] The invention provides a system for producing an optimized, tetrahydrocurcumin-loaded nanolipid carrier for intranasal administration to improve drug uptake in the brain and therapeutic efficacy. The system combines controlled lipid melting, surfactant-mediated emulsification, high-shear mixing, and cooling-induced nanoparticle solidification to form stable nanolipid carriers (NLCs) with targeted nanosize and high drug loading. Using a Box-Behnken optimization design, the system determines optimal formulation parameters to achieve a maximum drug loading of approximately 87.883% and a particle size of approximately 131.05 nm. These properties contribute to improved solubility, protection against degradation, and increased retention of THC within the lipid matrix.

[0004] The NLCs produced in the system also exhibit a sustained release profile according to the Higuchi model, indicating diffusion-controlled release and thus a prolonged therapeutic effect. The formulation is specifically optimized for intranasal administration and allows non-invasive access to cross the blood-brain barrier. Nasal ciliotoxicity studies confirm the formulation's complete safety for the mucosa. The system therefore enables stable, efficient, and targeted delivery of tetrahydrocurcumin for the treatment of neurodegenerative diseases. Detailed description

[0005] The system comprises a lipid processing unit in which solid and liquid lipids are fused under controlled temperature to form a homogeneous lipid phase suitable for embedding tetrahydrocurcumin. This lipid phase ensures sufficient solubilization of the hydrophobic active ingredient and protects it from environmental influences. A separate aqueous phase containing surfactants is prepared to stabilize the emulsion droplets formed during nanoparticle production.

[0006] The molten lipid phase is introduced into the aqueous phase under high shear to create a coarse emulsion. The system allows for precise control of mixing speed, surfactant concentration, and temperature to influence droplet size. Subsequent homogenization and rapid cooling promote the solidification of the lipid droplets into stable nanolipid carriers that encapsulate tetrahydrocurcumin.

[0007] The system's integrated optimization module uses the Box-Behnken method to determine the optimal values ​​of the key formulation variables. This statistical approach ensures high encapsulation efficiency, a suitable particle size, and favorable stability properties. The optimized formulation produces nanoparticles with a mean diameter of approximately 131 nm and an encapsulation efficiency of nearly 88%, enabling efficient drug delivery for intranasal administration.

[0008] The resulting nanolipid carriers are investigated in in vitro studies with regard to their release behavior. The release profile follows the Higuchi model and confirms that the release mechanism is primarily diffusion-controlled by the lipid matrix. This controlled release allows for prolonged exposure of the neurons to the drug, thus improving pharmacodynamic efficacy.

[0009] For intranasal application, the system ensures that the formulation maintains the required viscosity, stability, and mucosal compatibility. The NLC dispersion is designed to enable rapid absorption through the nasal mucosa and direct transport to the brain via the olfactory and trigeminal pathways. This approach bypasses the blood-brain barrier and significantly improves drug delivery to nerve tissue.

[0010] Nasal ciliotoxicity studies conducted with the system confirm that the formulation neither damages nor irritates the nasal mucosa, demonstrating its safety with repeated use. These studies confirm the suitability of the NLCs for non-invasive administration.

[0011] The system also ensures the physicochemical stability of the formulation during storage without significant aggregation or drug release. This stability is essential for long-term therapeutic efficacy.

[0012] Overall, the invention offers a technologically advanced platform for the production of tetrahydrocurcumin-loaded nanolipid carriers optimized for intranasal administration, combining high encapsulation efficiency, delayed release, safety, and improved potential for targeted brain delivery.

Claims

[1] A system for the production of tetrahydrocurcumin-loaded nanolipid carriers, consisting of modules for melting, emulsifying, homogenizing and cooling lipids, configured to produce nanoparticles with controlled size and high encapsulation efficiency. [2] System according to claim 1, wherein the formulation parameters are optimized using a Box-Behnken design to achieve a particle size of approximately 131 nm and an encapsulation efficiency of approximately 87%. [3] System according to claim 1, wherein the nanolipid carriers exhibit sustained drug release according to Higuchi diffusion kinetics. [4] A dosage formulation containing the nanolipid carriers produced according to any one of claims 1 to 3, which offers improved targeting accuracy in the brain and safety confirmed by nasal ciliotoxicity studies.