Synthesis and characterization of a colloidal novel folic acid–β-cyclodextrin conjugate for targeted drug delivery

Abstract

A novel folic acid-b-cyclodextrin (b-CD) conjugate was synthesized and preliminarily characterized by 1H NMR, ESI-MS, and MALDI-MS. 1H NMR shows the presence of a-and c-conjugates which are generated by b-CD linkage in turn with both carboxylic functions of folic acid. Moreover ROESY evidences supramolecular interactions between the benzene ring of the folic acid and the b-CD cavity. DOSY suggests that ethylenediamine derived b-CD-folic acid forms a colloidal dispersion difficult to purify from free folic acid. An analysis of self-diffusion coefficient (Ds) of the three species (a-, cconjugates, and free folic acid) and relaxation times (T1 and T2) is reported to tentatively explain the colloidal behaviour of the new species in an aqueous solution.

Review: Cyclodextrin Inclusion Complexes Probed by NMR Techniques

“…Besides the applicability of this technique to measure diffusion coefficients and association constants, DOSY experiments with cyclodextrins can be used with other techniques to predict enantiomeric discrimination , to predict drug diffusion with polymeric CD (Bakkour et al, 2006), to conclude by the formation of conjugates with CDs, as for example the conjugate between CD and folic acid, studied by Clementi et al (Clementi et al, 2010), etc. In our group, the complexes of Minoxidil (MNX) and CD was investigated by DOSY using the pulse sequence GCSTESL (DOSY Gradient Compensated was Stimulated Echo with Spin Lock), 25 different amplitudes of pulse gradients in each experiment with the parameters pw = 6.1s; at = 3.3 s; d1 = 3.0 s; nt = 32; lb = 0.2 Hz.…”

Monitoring the functionalization of single-walled carbon nanotubes with chitosan and folic acid by two-dimensional diffusion-ordered NMR spectroscopy

“…In a recent application, Marega et al [21] used 1 H-2D DOSY spectroscopy to monitor the functionalization and purification of a carbon nanotube-polyethylene glycol (CNT-PEG) conjugate. There have been numerous publications on the characterization of various bioconjugates using 2D NMR techniques [22,23]. However, studies related to the characterization of CNT-FA conjugates using 2D NMR spectroscopy have yet to be published.…”

Synthesis, characterisation and photo-stability of a folate-modified β-cyclodextrin as a functional food additive

“…In the 13 [17]. There is no evidence of a supramolecular interaction between folic acid and the cyclodextrin cavity.…”

“…The proposed structure of 6-deoxy-6-[(1-(2-amino)ethylamino)folate]--cyclodextrin (CDEnFA) is given below in Figure 3. The synthesis of CDEnFA was first reported by Clementi et al with a 5% yield but the product was reported to contain three different forms of folic acid even after extensive purification by column chromatography [13]. Two isomers, α and γ, were formed by reaction of CDEn with the two FA carboxylic functions at C9 and C13 respectively and free folic acid was also reported to be present [13].…”

“…The synthesis of CDEnFA was first reported by Clementi et al with a 5% yield but the product was reported to contain three different forms of folic acid even after extensive purification by column chromatography [13]. Two isomers, α and γ, were formed by reaction of CDEn with the two FA carboxylic functions at C9 and C13 respectively and free folic acid was also reported to be present [13]. In this current study a method reported by Guo and Lee for the synthesis of a folatepolyethylenimine-polyethyleneglycol conjugate was modified by changing the reaction temperature and the molar ratio of reactants, introducing diethylether as a drying agent and recrystallising the product from water [14].…”