AN ECO-FRIENDLY THERMO-SENSITIVE INJECTABLE HYDROGEL WITH CERIUM OXIDE NANOPARTICLE AND NANO- CURCUM

Abstract

The aim of this invention focuses on the development of a thermosensitive injectable hydrogel for combined loading of cerium oxide nanoparticles and nano-curcumin in order to enhance PDT in cancer treatment. Hydrogel formulation allows for controlled delivery of therapeutic drugs to the target location and also helps in the controlled release of the same; cerium oxide nanoparticles enhance ROS generation during PDT while nano-curcumin has anti­inflammatory and anti-cancer properties. The hydrophilic attribute of the hydrogel ensures that it works at body temperature therefore ensuring localized and controlled release of the drug. This co-loaded method solves critical limitations in conventional PDT techniques, providing increased effectiveness while reducing systemic toxicity.

Specification

Background of the Invention: Photodynamic therapy (PDT) involves the use of light-activated chemicals called photosensitizers which upon illumination generate ROS and cause the death of cancer cells [1]. Despite these circumstances PDT can be considered as non-invasive therapeutic methods Several problems were indicated which are inherent in PDT, for example, low bioavailability of the photosensitizer, in the tumor area, low specificity for tumors, and short treatment effect because of high rate of the "drug removal from the body (Figure-1) [2]-
Current Challenges in PDT: Limited Stability and Targeting: Most photosensitizers are lipophilic and hence they exhibit low solubility and rapidly get eliminated from the circulation. Consequently, achieving adequate concentrations at-the tumor site to exert therapeutic effect are often difficult to attain.
Systemic Toxicity: This may lodge in healthy tissues and when exposed to light, may produce some undesirable side effects.
Poor Tumor Penetration: Conventional PDT has limited ability to penetrate deeper into the tissue so in bigger or more malignant tumours, conventional PDT is ineffective [3].
To overcome these limitations, several nanomaterials, hydrogels and drug delivery techniques have been studied by the researchers. However, no approach has attained peak efficiency by combining targeted delivery, increased ROS production, improved drug stability, and low side effects. This innovation tackles these constraints by incorporating cerium oxide nanoparticles (CeOi NPs) and nanocurcumin into a thermosensitive hydrogel. Cerium oxide nanoparticles act as ROS producers and modulators, whereas nano-curcumin is a therapeutic and stabilizing agent. The thermosensitive hydrogel enables targeted and controlled release, considerably increasing the therapeutic efficiency of PDT while reducing adverse effects.
Summary of the Invention: The invention includes a composition of a thermo-sensitive injectable hydrogel encapsulating both cerium oxide nanoparticles and nano-curcumin and especially formulated to enhance the effectiveness of photodynamic therapy for cancer. The co-loaded hydrogel exhibits the following important characteristics: Thermosensitivity: This is made possible due to the fact that, after injection into the body, the hydrogel is in a liquid solution form at room temperature and it acts like a gel at the physiological temperature. This makes ensure that therapeutic molecules are deposited in a spatial selective and in a continuous fashion at the tumor site [4].
The cerium oxide nanoparticles: This work as photosensitizers, meaning the production of ROS is enhanced during the light irradiation. Further, the interaction of cerium oxide with nano-curcumin also enhances the therapeutic potentiality of the formulation [5], Curcumin's Dual Role: Nano-curcumin - a potent natural antioxidant and anti-inflammatory plays a synergistic effect with cerium oxide nanoparticles to enhance both the killing rate of cancer cells and the delivery system's stability of the hydrogel formulation at the same time [6].
Biocompatibility and Toxicity: Cerium oxide is safe and non-toxic and curcumin is also safe when used in nano form meaning that the combination of both is safe for human use thus minimizes on the side effects. The hydrogel matrix further reduces systemic toxicity by concentrating medication release [7].
The idea provides a unique approach to cancer treatment by addressing the shortcomings of current photodynamic therapy systems, such as poor bio distribution, quick clearance, and a lack of selectivity.


Cerium oxide nanoparticles: CeO2 NPs contain cerium which has an ability to switch between Ce3+ and Ce4+ oxidation states and as a result the material has found to possess peculiar redox properties.
These redox capabilities make cerium oxide nanoparticles perfect candidates for enhancing ROS production during the light activation process that forms a core necessity of PDT. CeO2 NPs may remove free radicals reducing oxidative stress for the normal tissues and generate ROS at the tumor site whenever exposed to light.
Synthesis of CeO2 nanoparticles: Among these, the sol-gel process is very favourable and the microemulsion process is very promising. These approaches provide homogeneous particle size and large surface area, which are required for effective ROS formation [8,9]. 2. Nano-Curcumin: Curcumin isolated from the turmeric has a unique propensity towards cancer and can be said to possess the cancer cell growth inhibition property along with the ability to arrest cancer cell's metastasis. However, because the fact solubility is high fats and low in water as well as poor ' bioavailability it has found its limited use in medical applications. All these challenges can be checked by nano-encapsulation of curcumin in as process enhances its solubility and stability in addition to its bio availability.
There are three methods of making nanocurcumin including the nanoprecipitation method and the emulsion method. These techniques assist in this process of reducing the particle size of curcumin thus enhancing the cancer cell penetrative capacity of the particle [10]. 3. Thermo-Sensitive Injectable Hydrogel: Hydrogels consist of polymers; these are Polylactic co- glycolic acid (PLGA), polyethylene glycol (PEG) both of which are biodegradable and biocompatible.
It also demonstrates stimuli sensitive nature where it is still in liquid state but on inducing gelation at 37° C which is body temperature [4].
Such a temperature-dependent transition can allow for easy infusion to the tumor site before gelling and confining the nanoparticles and curcumin to the tumor environment.


Preparation of the Co-loaded Hydrogel: The co-loaded hydrogel is prepared in many steps: 1. Synthesis of Cerium oxide nanoparticles and nano-curcumin: The samples of cerium oxide nanoparticles were synthesised through hydrothermal process and in the next step the sample was purified. For stability to be attained, it is understood that synthesis of nano-curcumin occurs through nanoprecipitation after which freeze filtration is conducted [l 1,12], 2. Hydrogel Matrix Formation: The hydrogel foundation is produced by either dissolving PLGA or PEG in a solution like DMSO or water. Subsequently the cerium oxide nanoparticles and nano-curcumin are dispersed into the hydrogel matrix by ultrasonication or homogeneous mixing Figure. 2 [ 13]. 3. Sterilization and storage: Before using the produced hydrogel, in vivo, it undergoes sterilization where methods that are used include UV sterilization or autoclaving to ensure no contaminants. In order to avoid fluctuations in the stability of the product, the finished product is stored at low temperatures [14].
Application Mechanism: Copolymer hydrogels can be injected and gelation occurs at physiological temperature helping to form a long-acting depot at the tumor site. Remarkably, cerium oxide nanoparticles, when illuminated, generate ROS that induces oxidative-stress to the cancer cells and kills them upon exposure to light. Nano-curcumin has the ability to decrease the level of inflammation that is present in the body as well as the ability to be anti­cancer. Thus, the hydrogel matrix is used to release both therapeutic drugs slowly and for an extended period



Engineered injectable hydrogel for cancer's two stimuli-responsive photodynamic therapy with cerium oxide nanoparticles and nano-curcumin.
Claim 2: A technique of synthesizing hydrogels, containing cerium oxide nanoparticles and nano- curcumin within a polymeric matrix which is biodegradable in nature.
Claim 3: Cerium oxide nanoparticles which may be able to catalyse ROS in treating the cancer through performing the photodynamic therapy.
Claim 4: The increase of the effectiveness of the photodynamic therapy against cancer using nano-
curcumin.

The reason for this achievement, which marks a very significant advancement in the treatment of cancer, is that it was caused by a thermo-sensitive hydrogel that was co-encapsulated with nano- curcumin and nano-cerium oxide nanoparticles. The development of a hydrogel that is very sensitive
-Nov-2024/138506/202441089874/Form 2(Title Page)
to temperature was the catalyst that made this achievement feasible. To improve the effectiveness of photodynamic therapy, the process is designed to increase the generation of reactive oxygen species (ROS) and to make it easier for medicine to be released at a later time. One additional benefit of the targeted delivery strategy is that it lessens the overall toxicity of the medication, which establishes it as a potentially helpful instrument for the treatment of cancer.

Documents