BIO-BASED CHITOSAN DERIVATIVES FOR DRUG DELIVERY: A THEORETICAL STUDY

Nanoparticles (NPs) have an outstanding position in pharmaceutical, biological, and medical disciplines. Polymeric NPs based on chitosan (CS) can act as excellent drug carriers because of some intrinsic beneficial properties including biocompatibility, biodegradability, non-toxicity, bioactivity, easy preparation, and targeting specificity. Drug transport and release from CS-based particulate systems depend on the extent of cross-linking, morphology, size, and density of the particulate system, as well as physicochemical properties of the drug. All these aspects have to be considered when developing new CS-based NPs as potential drug delivery systems [1-5]. This theoretical study delves into the use of bio-based chitosan derivatives in drug delivery systems. Chitosan, a biopolymer derived from chitin, offers several advantageous properties, including biocompatibility, biodegradability, and mucoadhesive qualities. Modifying chitosan through chemical or physical methods enhances its solubility, bioavailability, and ability to interact with various drug molecules, making it a suitable candidate for targeted and controlled drug delivery. The focus of this study is on the theoretical modeling and simulation of chitosan derivatives to evaluate their performance in drug release kinetics, bio-interactions, and efficacy in various delivery routes such as oral, transdermal, and injectable systems. Chitosan, derived from the deacetylation of chitin, has garnered attention due to its natural abundance and favorable properties. In its native form, chitosan has limited solubility in water, which restricts its application in drug delivery. However, chemical modifications lead to the creation of chitosan derivatives that improve solubility, interaction with drugs, and bioavailability. Theoretical studies using computational models are essential for understanding these interactions at a molecular level, enabling the prediction of drug release patterns and the behavior of the drug-polymer system [6-9]. In this work, DFT (Density Functional Theory) was used to study hydrophobic, amphiphilic, ionic chitosan copolymers, and derivatives with specific substituents, as well as crosslinked chitosan derivatives, totaling over 20 different compounds. Reactivity descriptors were calculated, and specific functional groups that are experimentally functionalized for certain medical purposes or for the development of agricultural products were identified. The correlation between band gap width and biological activity was also demonstrated. The theoretical modeling of bio-based chitosan derivatives provides valuable insights into their potential as drug delivery systems. Through computational simulations and kinetic models, it is possible to predict and optimize their performance, thereby enhancing the development of novel delivery systems for various therapeutic agents. References 1. K. Akhiro, T. Kenjiro, S. Yasuo, M. Tsutomu. J. Am. Chem. Soc., 2009, 131, 6050–6051. 2. M.D. Shin, S. Shukla, Y.H. Chung, V. Beiss, S.Kh. Chan, O.A. Ortega-Rivera, D.M. Wirth, A. Chen, M. Sack, J.K. Pokorski, N. Nat Nanotechnol., 2020, 15, 646–655. 3. A.E. Nel. ACS Nano, 2021, 15, 5793–5818. 4. D. Yang. Int. J. Nanomed., 2021, 16, 623–649. 5. Z. Tang, X. Zhang, Y. Shu, M. Guo, H. Zhang, W. Tao. Nano Today., 2021, 36, 101019. 6. Z. Tang, N. Na Kong, X. Zhang, Y. Liu, P. Hu, Sh. Mou, P. Liljeström, J. Shi, W. Tan, J.S. Kim, Y. Cao, R. Langer, K.W. Leong, O.C. Farokhzad, W. Tao. Nat. Rev. Mater., 2020, 5, 847–860. 7. Z. Zhang, Z. Tang, N. Farokhzad, T. Chen, W. Tao. Matter., 2020, 3, 1818–1820. 8. J.A. Loureiro, M.C. Pereira. Pharm., 2020, 12, 903. 9. I. Dumbuya, A.M. Pereira, I. Tolaymat, A. Al Dalaty, B. Arafat, M. Webster, B. Pierscionek, M. Khoder, M. Najlah. Nanomater., 2024, 14, 1133.