2 research outputs found
Self-assembled cationic #-cyclodextrin nanostructures for siRNA delivery
Functionalized cyclodextrin molecules assemble into a wide variety of superstructures in solution, which are of interest for drug delivery and other nanomaterial and biomaterial applications. Here we use a combined simulation and experimental approach to probe the coassembly of siRNA and cationic cyclodextrin (c-CD) derivatives into a highly stable gene delivery nanostructure. The c-CD form supramolecular structures via interdigitation of their aliphatic tails, analogous to the formation of lipid bilayers and micelles. The native conformation of siRNA is preserved by the encapsulating c-CD superstructure in an extensive hydrogen-bonding network between the positively charged side arms of c-CD and the negatively charged siRNA backbone. The stability of the complexation is confirmed using isothermal titration calorimetry, and the experimental/simulation codesign methodology opens new avenues for creation of highly engineerable gene delivery vectors
Nanoscaled Zinc Pyrazolate Metal–Organic Frameworks as Drug-Delivery Systems
This
work describes synthesis at the nanoscale of the isoreticular
metal–organic framework (MOF) series ZnBDP_X, based on the
assembly of Zn<sup>II</sup> metal ions and the functionalized organic
spacers 1,4-bisÂ(1<i>H</i>-pyrazol-4-yl)-2-X-benzene (H<sub>2</sub>BDP_X; X = H, NO<sub>2</sub>, NH<sub>2</sub>, OH). The colloidal
stability of these systems was evaluated under different relevant
intravenous and oral-simulated physiological conditions, showing that
ZnBDP_OH nanoparticles exhibit good structural and colloidal stability
probably because of the formation of a protein corona on their surface
that prevents their aggregation. Furthermore, two antitumor drugs
(mitroxantrone and [RuÂ(<i>p</i>-cymene)ÂCl<sub>2</sub>(pta)]
(RAPTA-C) where pta = 1,3,5-triaza-7-phospaadamantane) were encapsulated
within the pores of the ZnBDP_X series in order to investigate the
effect of the framework functionalization on the incorporation/delivery
of bioactive molecules. Thus, the loading capacity of both drugs within
the ZnBDP_X series seems to directly depend on the surface area of
the solids. Moreover, ligand functionalization significantly affects
both the delivery kinetics and the total amount of released drug.
In particular, ZnBDP_OH and ZnBDP_NH<sub>2</sub> matrixes show a slower
rate of delivery and higher percentage of release than ZnBDP_NO<sub>2</sub> and ZnBDP_H systems. Additionally, RAPTA-C delivery from
ZnBDP_OH is accompanied by a concomitant and progressive matrix degradation
due to the higher polarity of the BPD_OH ligand, highlighting the
impact of functionalization of the MOF cavities over the kinetics
of delivery