Targeted Drug Delivery Systems for Cancer Therapy

Antonio Clementi, Dublin Institute of Technology
Christine O'Connor, Dublin Institute of Technology
M McNamara
A Mazzaglia, University of Messina
MC Aversa, University of Messina
A Giuffrida, University of Catania

Document Type Article


The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. β-CD has been widely used in the early stages of pharmaceutical applications because of its ready availability and its cavity size suitability for a wide range of drugs. Chemical modification of β-CD has proven to enhance aqueous solubilisation, microbiological stability and reduced toxicity in previous studies. 1 Folate Receptors are over-expressed in several human cancers including ovarian, breast and renal carcinomas. This property has been utilised to develop tumour-selective anti-neoplastic drugs. Folate has been bound to chemotherapeutic drugs and since tumour cells have a huge appetite for folate, their folate receptors ‘pull’ the drug-folate conjugate towards the tumour site. However the direct conjugation of folate to the bioactive drug can lead to loss of targeting or alter the function of the conjugate. Folate-cyclodextrin bioconjugates have been prepared with polyethylene glycol (PEG) linkers; however this conjugate partially prevents drug degradation.2,3 This study describes the synthesis and characterisation (UV-Vis, Emission, IR, Raman, NMR, MALDI-MS and ESI-MS) of a novel folate-cyclodextrin bioconjugate. As mentioned previously it was found that direct conjugation of folate to the bioactive molecules led to loss of targeting or an alteration of the function of the conjugate and most of the conjugates to date cannot be further modified to improve targeting or anti-tumour activity.4-8 Preliminary biological evaluation of the tumour targeting device will be discussed.