A photochemical approach for controlled drug release in targeted drug delivery

Abstract

Photochemistry provides a unique mechanism that enables the active control of drug release in cancer-targeting drug delivery. This study investigates the light-mediated release of methotrexate, an anticancer drug, using a photocleavable linker strategy based on o-nitrobenzyl protection. We evaluated two types of the o-nitrobenzyl-linked methotrexate for the drug release study and further extended the study to a fifth-generation poly(amidoamine) dendrimer carrier covalently conjugated with methotrexate via the o-nitrobenzyl linker. We performed the drug release studies by using a combination of three standard analytical methods that include UV/vis spectrometry, 1H NMR spectroscopy, and anal. HPLC. This article reports that methotrexate is released by the photochemical mechanism in an actively controlled manner. The rate of the drug release varies in response to multiple control parameters, including linker design, light wavelength, exposure time, and the pH of the medium where the drug release occurs.

A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging

“…Each showed a λ max at 346 nm ( ε = 5,950 ( 1 ); ε = 4,292 ( 2 ) M −1 cm −1 ) which is slightly longer than the λ max value of 340 nm for a conventional ONB cage terminated with benzylic alcohol. [18b] This bathochromic shift might be attributable to the effect of the sulfur atom placed on the TNB cage which is less electron withdrawing than the benzylic oxygen in the ONB system. [28] The photolysis of TNB cages 1 and 2 was performed by UVA exposure (365 nm), and its progress was monitored by 1 H NMR spectroscopy, UV–vis spectrometry and UPLC, each providing evidence supportive of the cleavage mechanism proposed in Figure 3a.…”

“…UVA is less toxic to most mammalian cells than shorter UVB and UVC, and thus has served as a tool for active control in chemical biology such as protein activation, [3a, 5a, 15] optogenetics, [4a, 4c, 16] and photochemical internalization of biomacromolecules. [17] More recently, applications of light-controlled mechanisms for drug release [13] have been developed by numerous laboratories including ours in the design of prodrugs and drug delivery systems for various therapeutic agents including olaparib (AZD-2281), [11e] melphalan, [11f] methotrexate, [18] doxorubicin (Dox), [10b, 10c, 19] paclitaxel (taxol), [20] 5-fluorouracil, [21] tamoxifen, [4a, 8, 16] and ciprofloxacin. [22] However, efficient implementation of photocage molecules for such applications [13] is often challenging due in part to the synthetic complexity involved in drug and/or reporter conjugation which requires a multistep process.…”

Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates

“…UV–vis spectral traces (top, inset) acquired over the irradiation time course showed a notable change in the absorbance at 280 nm which reflects photocleavage of the ONB linker (quantum efficiency Φ = 0.29) 32 as observed in other drug release systems. 32–34 These analyses demonstrate the effectiveness of UV in the active control of ciprofloxacin release from its ONB photocaged form on LPS-targeted dendrimers 3 and 4 .…”

Experimental and theoretical investigations in stimuli responsive dendrimer-based assemblies

“…The o -nitrobenzyl ether moiety has also been used to directly cage drug molecules, such as doxorubicin 100 and methotrexate 101 using the dendritic scaffold (Fig. 10).…”