(T1230-01-04) Development and Characterization of Solid Lipid Nanoparticles Encapsulating Curcumin for Targeted Therapy of Mucosal-Barrier Associated Cancers

Purpose: Curcumin is known for its anti-inflammatory and anti-infectious properties. Several studies reported curcumin’s antitumor activity on breast cancer, lung cancer, head and neck squamous cell carcinoma, prostate cancer, and brain tumors, showing its capability to target multiple cancer cell lines. Curcumin has displayed anticancer properties in mucosal layer cancers such as mouth, cervical, anal, and skin cancers, alongside its capacity to reduce inflammation in the inflamed tissues characteristic of these conditions. In spite of all the above-mentioned advantages, curcumin’s applications are limited due to its low water solubility which results in poor oral bioavailability and also low chemical stability. A primary challenge in topical curcumin delivery is the burning sensation reported by patients, along with adverse effects such as discomfort and itching especially in the mucosal layers. To address these side effects, we hypothesize that solid lipid nanoparticle (SLN) encapsulation of curcumin will mask the non-compatible parameters of curcumin in the mucosal areas of administration. We also hypothesize is that our formulation will enhance the tolerability, provide controlled release, and improve drug stability. To achieve our objective, we formulate SLNs containing curcumin, utilizing cocoa butter as the biocompatible lipid for encapsulation. The moisturizing qualities of cocoa butter will provide a smooth texture, facilitating easy application followed by characterizing the physicochemical properties of the SLNs. In the future, these SLNs can be developed as targeted drug delivery systems for mucosal cavities via vaginal and rectal routes. Utilizing topical curcumin through nanotechnology in these routes provides exciting opportunities for enhanced targeted delivery to mucosal layers, offering direct access to the disease site, thus serving as excellent options for patient preventive or treatment options.

Methods: We used hot homogenization technique to produce curcumin solid lipid nanoparticles. We used generally recognized as safe (GRAS) excipients in the formulation of the SLNs using cocoa butter as a base. Cocoa butter is liquified by melting above its melting point to generate an organic phase, within which the curcumin is dispersed. Then we add water and glycerine which acts a cryoprotectant, which makes our aqueous phase along with addition of hydrophobic and hydrophilic emulsifiers. This mixture is subjected to high-speed homogenization for various cycles. The SLN formulation was freeze-dried using a Lyophilizer to obtain the dry product leading to the formation of nano-lipid particles. We test the nanoparticles to evaluate their pH, size, PDI, zeta potential, encapsulation efficiency, percent yield, cytotoxicity testing and release studies.

Results: The SLNs were found to melt at body temperature (37 degree Celsius) within 10 minutes. The pH for rectal SLNs was neutral (pH 7) and pH for vaginal SLNs was adjusted to 4. The characterization results revealed the particle size to be 843.8 nm; PDI of 0.641 and zeta potential to be 0.179 mV.

Conclusion: In summary, we utilized Curcumin, a naturally derived herb known for its minimal side effects, to successfully develop SLNs aimed at mitigating the local irritation often associated with curcumin use. Our primary objectives were to enhance stability and protect against degradation. Given curcumin's limited aqueous solubility, encapsulation within SLNs offered a means to achieve controlled drug release and significantly elevate drug loading. Consequently, we increased curcumin's bioavailability owing to the small particle size and expansive surface area of SLNs. These non-irritating SLNs are used for further formulation into targeted drug delivery systems applicable to mucosal orifices such as vaginal, rectal, or buccal routes. Utilising these pathways can circumvent first-pass metabolism, enhance absorption via the highly vascular nature of mucosal tissues, and foster improved patient compliance for treatment of mucosal barrier associated cancers.

References: 1. Aggarwal, Bharat & Kumar, Anushree & Bharti, Alok. (2002). Anticancer Potential of Curcumin: Preclinical and Clinical Studies. Anticancer research. 23. 363-98.
2. Rasha Shtay, Chin Ping Tan, Karin Schwarz, Development and characterization of solid lipid nanoparticles (SLNs) made of cocoa butter: A factorial design study, Journal of Food Engineering, Volume 231,2018
3. Ban C, Jo M, Park YH, et al. Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles. Food Chem. 2020;302:125328. doi:10.1016/j.foodchem.2019.125328


Preparation of Curcumin SLN using Hot homogenization method


Characterization results for Curcumin loaded Solid Lipid Nanoparticles