Capecitabine loaded potato starch-chitosan nanoparticles: A novel approach for targeted therapy and improved outcomes in aggressive colon cancer

Within the context of nanotechnology, there has been a groundbreaking advancement in the field of drug delivery systems[1], [2], [3]. This development exploits the unique characteristics of nanoparticles, which distinguish them from larger quantities of the same material[4]. This significant change offers exceptional prospects for the development of novel drug delivery systems distinguished by enhanced effectiveness and accuracy[5].

Cellulose, chitosan, and starch are natural polysaccharides that are being increasingly used as the basis for creating nanoparticles[6], [7], [8], [9], [10]. These polysaccharides provide desirable qualities such as biocompatibility, biodegradability, and renewability[11]. The significant presence of potato starch, obtained from Solanum tuberosum, is particularly noteworthy in regions such as India, where an annual production of 2.5 million tonnes is prevalent[11], [12]. This provides a compelling opportunity for the synthesis of nanoparticles[13].

Chitosan, a highly regarded substance derived from chitin through deacetylation, stands out as a biopolymer that is both biodegradable and resistant to degradation[14]. Novel methods of crosslinking, such as reductive alkylation using a polyaldehyde obtained from the oxidation of β-cyclodextrin[15], have been investigated to enhance the structural strength of chitosan. The result is the formation of crosslinked nanoparticles made from polysaccharides, which have great potential for improving the solubility, bioavailability, and retention duration of drugs[16]. The growing fascination with polysaccharide-based polymeric nanoparticles signifies the beginning of a new era in drug delivery methods[17]. These nanoparticles provide benefits such as enhanced therapeutic effectiveness, safeguarding against biological breakdown, and the capability to control the rate at which drugs are released. These characteristics make nanoparticles highly suitable for delivering therapeutic agents, especially in the complex field of cancer treatment[18].

Colorectal cancer[19], a field requiring novel therapeutic strategies, ranks as the second most common cancer in women and the third most common in men. Precise drug delivery to tumour locations is crucial in cancer treatment, especially in suppressing angiogenesis induced by vascular endothelial growth factor (VEGF)[20].

Capecitabine, a prodrug that metabolises into 5-fluorouracil (5-FU) in the body, is a powerful weapon against colorectal cancer[21]. It works by blocking thymidylate synthase and stopping the growth of cancer cells.

Nanotechnology offers a promising approach to tackle drug delivery difficulties and improve treatment results. The use of biodegradable, polysaccharide-based nanoparticles to encapsulate chemotherapeutic drugs has become popular due to its ability to enhance drug release profiles and enhance biocompatibility.

Capecitabine, the precursor of 5-fluorouracil (5-FU), face significant obstacles such as limited ability to be absorbed by the body, significant toxicity throughout the body, and a clear inability to differentiate between diseased and healthy tissues. The conversion of capecitabine into its active metabolite, 5-FU, is crucial for its effectiveness in treating cancer. However, the rapid breakdown of 5-FU in the bloodstream significantly reduces the drug's concentration at the tumour site, unintentionally creating an environment that promotes negative effects on healthy tissues. In addition, the traditional method of administering Capecitabine orally is characterised by inconsistent rates of absorption, hence increasing its therapeutic constraints. The incorporation of Capecitabine into nanoparticles presents a promising solution to overcome these constraints. This study focuses on synthesising Capecitabine-loaded nanoparticles using potato starch and chitosan through the Ionotropic gelation process[22], [23].

This novel methodology holds the potential to enhance the administration of drugs by: (1) providing protection to Capecitabine against premature degradation, thereby increasing the concentration of the drug that is available for use at the tumour site; (2) allowing for precise targeting of cancer cells by modifying nanoparticles to recognise specific receptors on cancer cells, thereby reducing the overall toxicity of the drug; and (3) enabling a controlled release mechanism, which could potentially balance the effectiveness of the drug with minimal negative effects. The incorporation of biocompatible and biodegradable substances, such as potato starch and chitosan, in the production of nanoparticles loaded with Capecitabine, using methods like Ionotropic gelation, presents a promising approach to overcome the existing constraints in colorectal cancer treatment. This methodology not only exhibits potential for a focused drug delivery model but also for prolonged drug release patterns and enhanced anticancer efficacy, representing a notable advancement towards the enhancement of chemotherapeutic interventions.

The nanoparticles show potential for treating colon cancer by acting as a drug delivery system that is both biodegradable and biocompatible. Our research involves a comprehensive strategy that includes analysing antioxidants, monitoring the release of drugs, evaluating the anticancer activity in Balb/c albino mice[24], and studying the anticancer activity in HT-29 cell lines in a laboratory setting. In our investigation, we focus on histopathological changes[25], cellular absorption processes, cell migratory kinetics, tube-forming assays, reactive oxygen species (ROS) production, and cellular death as important aspects.

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