Abstract
The growing incidence of global lung cancer cases against successful treatment modalities has increased the demand for the development of innovative strategies to complement conventional chemotherapy, radiation, and surgery. The substitution of chemotherapeutics by naturally occurring phenolic compounds has been touted as a promising research endeavor, as they sideline the side effects of current chemotherapy drugs. However, the therapeutic efficacy of these compounds is conventionally lower than that of chemotherapeutic agents due to their lower solubility and consequently poor intracellular uptake. Therefore, we report herein a hydrophobically modified chitosan nanoparticle (pCNP) system for the encapsulation of protocatechuic acid (PCA), a naturally occurring but poorly soluble phenolic compound, for increased efficacy and improved intracellular uptake in A549 lung cancer cells. The pCNP system was modified by the inclusion of a palmitoyl group and physico-chemically characterized to assess its particle size, Polydispersity Index (PDI) value, amine group quantification, functional group profiling, and morphological properties. The inclusion of hydrophobic palmitoyl in pCNP-PCA was found to increase the encapsulation of PCA by 54.5% compared to unmodified CNP-PCA samples whilst it only conferred a 23.4% larger particle size. The single-spherical like particles with uniformed dispersity pCNP-PCA exhibited IR bands, suggesting the successful incorporation of PCA within its core, and a hydrophobic layer was elucidated via electron micrographs. The cytotoxic efficacy was then assessed by using an MTT cytotoxicity assay towards A549 human lung cancer cell line and was compared with traditional chitosan nanoparticle system. Fascinatingly, a controlled release delivery and enhanced therapeutic efficacy were observed in pCNP-PCA compared to CNP, which is ascribed to lower IC50 values in the 72-h treatment in the pCNP system. Using the hydrophobic system, efficacy of PCA was significantly increased in 24-, 48-, and 72-h treatments compared to a single administration of the compound, and via the unmodified CNP system. Findings arising from this study exhibit the potential of using such modified nanoparticulate systems in increasing the efficacy of natural phenolic compounds by augmenting their delivery potential for better anti-cancer responses.
Highlights
Despite improvements in the medical field nowadays, cancer remains one of the most studied diseases due to its complexity and continually increasing incidence rate throughout the decades
These Food and Drug administration (FDA)-approved drugs can give rise to these side effects frequently due to the high dose administration and non-specific destruction of these chemotherapy agents, where the non-specific cytotoxicity often resulted in low tumor specificity and high toxicity, leading to various concomitant side effects [3]
A similar trend was revealed by palmitic acid to synthesize hydrophobically modified-chitosan nanoparticles (pCNP) where the size of initial pCS at no TPP addition was 4560.33 ± 614.17 nm, dramatically dropped to 289.83 ± 8.92 nm at 50 μL TPP volume addition, and gradually decreased until it reached its smallest size of 90.23 ± 2.67 nm at 200 μL TPP addition
Summary
Despite improvements in the medical field nowadays, cancer remains one of the most studied diseases due to its complexity and continually increasing incidence rate throughout the decades. According to the National Cancer Institute, the use of such drugs in anticancer therapy will frequently confer unwanted side effects, such as hair loss, fatigue, anemia, appetite changes and nausea, and vomiting, which further hinder the recovery of patients. These Food and Drug administration (FDA)-approved drugs can give rise to these side effects frequently due to the high dose administration and non-specific destruction of these chemotherapy agents, where the non-specific cytotoxicity often resulted in low tumor specificity and high toxicity, leading to various concomitant side effects [3]. Alternatives for these chemotherapy agents are needed to avoid unpleasant side effects for the patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
