Catechol-Functionalized Alginate Nanoparticles as Mucoadhesive Carriers for Intravesical Chemotherapy
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Research Article Catechol-Functionalized Alginate Nanoparticles as Mucoadhesive Carriers for Intravesical Chemotherapy Nitjawan Sahatsapan,1 Tanasait Ngawhirunpat,1 Theerasak Rojanarata,1 Praneet Opanasopit,1 and Prasopchai Patrojanasophon1,2
Received 24 April 2020; accepted 7 July 2020 Abstract.
This research aimed to synthesize and evaluate mucoadhesive catecholfunctionalized alginate (Cat-Alg) nanoparticles (NPs) for bladder cancer. Cat-Alg was synthesized using coupling chemistry, and the structure was verified using NMR and FT-IR. Cat-Alg NPs were generated by ionic gelation between the synthesized Cat-Alg and calcium chloride. Garcinia mangostana L. extract (GM extract) was entrapped into the NPs during particle formation. The physical characteristics, mucoadhesive properties, drug loading and release, cellular uptake, and anticancer activity of the GM extract-loaded NPs were investigated. The Cat-Alg NPs were spherical with sizes in the range of 155–186 nm. The slightly negative surface charge of the NPs provided them with excellent stability. The Cat-Alg NPs could be retained on a porcine bladder mucosa to a greater extent compared with unmodified Alg NPs. High loading efficiency (71.6%) and loading capacity (292 μg/mg) of GM extract in the NPs were achieved, and a constant release of GM extract was obtained for up to 8 h with zero-order kinetics. Moreover, the GM extract-loaded NPs were deposited in bladder tissue and accumulated in MB49 cells at a higher rate compared with GM extract suspension. In addition, the NPs could kill a mouse urothelial carcinoma cell line with low IC50. Therefore, these NPs have the potential to be a mucoadhesive drug delivery system for bladder cancer treatment. However, additional in vivo investigations are needed for clinical application in cancer treatment. KEY WORDS: alginate; catechol; mucoadhesive; Garcinia mangostana; nanoparticles.
INTRODUCTION Bladder cancer has been ranked as the ninth most frequently diagnosed cancer globally, attributing to 6.6% of all cancer cases (1,2). Systemically, treatment for bladder disease is generally unsuccessful as only a small amount of medication reaches the target area due to the bladder’s complicated anatomical features (3,4). Intravesical administration is one of the prevailing practices to manage bladder cancer. The effectiveness of intravesical therapy relies on the resident time and the amount of the drug that the urinary bladder can retain (3). Unfortunately, the chemotherapeutic agent can be washed out quickly while the bladder is emptying. This leads to a reduction in both the concentration and the amount of time the drug is retained in the bladder. Therefore, there is a need to further develop mucoadhesive Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-020-01752-7) contains supplementary material, which is available to authorized users. 1
Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand. 2 To whom correspondence should be addressed. (e–mail: patro
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