Light Sensitive Block Copolymer Cross Linked Nanoassemblies for Drug Delivery

Purpose:  To develop photosensitive cross-linked nanoassemblies (CNAs) for drug delivery to tumor tissue.

Methods:  Nanoparticles were developed from cinnamoyl Poly(ethylene glycol)-poly(aspartate hydrazide) [cinnamoyl PEG-Hyd] block copolymers. Cross-linking was achieved through the ultraviolet radiation-induced (λ = 254nm) photochemical dimerization of the cinnamoyl moiety.  The CNAs were characterized for size and stability and loaded with anticancer agent, doxorubicin.  Drug release studies were performed at physiological and tumor pH for various degrees of cross-linking.

Results:  UV-Vis Absorption spectra confirmed that cross-linking of the cinnamoyl PEG-Hyd block copolymer nanoassemblies was successfully carried out. Dynamic light scattering measurements showed consistent nanoparticle size and charge over a 0 to 4 hour range of UV exposures.  A new batch of cinnamoyl PEG-Hyd was synthesized; its purity was validated by gel permeation chromatography and ¹H-NMR analysis.  Doxorubicin was entrapped in the CNA via conjugation to the hydrazide bond.  Drug release profiles showed no significant difference between pH 7.4 and 6.0 for three different groups of CNAs (0 min, 12 min, and 120 min UV exposure).

Conclusions:  Stable CNAs were developed and loaded with doxorubicin, but no significant difference in drug release was established for tumor pH. This could be attributed to doxorubicin entrapment after cross-linking.