Interaction of Riboflavin-5-Phosphate With Liposome Bilayers

Introduction

A beam light at a visible or near infrared (NIR) wavelength to destroy the target cells bases photodynamic therapy (PDT) or a photodynamic reaction involving a light-sensitive substance (a photosensitizer) combined with the irradiation. It is emerging as a highly effective, non-invasive therapeutic approach in the struggle against cancer and other infectious diseases (Ma, Huang, Song, Chen, & Zhang, 2016). Despite the significant progress and scientific reports, PDT is yet to be established as an effective and safe technique to eradicate microbes and tumors (Konan, Gurny, & Allemann, 2002). Riboflavin-5-phosphate, also referred as vitamin B₂, is a potent antioxidant and is used as a supplement in chemotherapy due to its anti-carcinogenic properties (Ashoori & Saedisomeolia, 2017; Kandzija & Khutoryanskiy, 2017). In addition to the anti-carcinogenic properties, riboflavin has also reported as a potential photosensitizer for PDT. The photosensitive property of riboflavin has been investigated in eliminating tumor, ocular and skin and bacterial infections (Arboleda et al., 2014; Edwards, Barredo, Silva, De Ioannes, & Becker, 1999; Ion, 2007; Kashiwabuchi ., 2012; Khaydukov et al., 2016; Sato, Sakakibara, Hasegawa, Minami, & Tsuji, 2000; Shen ., 2017). However, the hydrophilic nature of riboflavin causes rapid clearance of the drug in the blood stream and lowers the intracellular absorption, thereby, reducing its therapeutic efficacy (Eloy et al., 2014). Liposome based carriers have been exploited to encapsulating hydrophilic drugs to prevent their rapid clearance and increase their circulation time upon administration. (Eloy et al., 2014; Pabst, Kučerka, Nieh, & Katsaras, n.d.; Torchilin, 2005; Xu, Khan, & Burgess, 2012).

Liposomes are self-assemblies of lipids, which are amphipathic in nature consisting of a hydrophilic head and a hydrophobic tail. Liposomes are characterized by a lipid bilayer surrounding aqueous core which self-assemble to give rise to an aqueous core (Gupta, Mandal, Ahmadibeni, Parang, & Bothun, 2011; Matos, Moutinho, & Lobão, 2012). Due to this unique structure, they are capable of entrapping both hydrophobic and hydrophilic molecules (Murthy, 2007). A variety of simple and economic methods such as dry film hydration, solvent exchange, electro formation methods have been investigated to form liposomes with variable size, surface charge, and number of bilayers (Patil & Jadhav, 2014). Addition of cholesterol improves the circulation of liposomes in the blood stream while providing the steric stabilization through increasing the rigidity of the bilayer (Tan, 2015). Although the efficacy of liposome encapsulated riboflavin-5-phosphate formulations has been reported (Ahmad et al., 2015; Ioniţă, Ion, & Cârstocea, 2003) the effects of interaction between the free-floating riboflavin-5-phosphate, a potent riboflavin derivative on the stability of liposome carriers remain unaddressed.