L-Arginine-Derived Polyamidoamine Oligomers Bearing at Both Ends β-Cyclodextrin Units as pH-Sensitive Curcumin Carriers

Abstract

The aza-Michael polyaddition of L-arginine and N,N′-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the β-cyclodextrin-end-terminated oligomers P3 and P5, which have been shown to encapsulate curcumin at both pH 7.4 and 4.5. After lyophilization, P3- and P5-curcumin complexes gave stable water solutions. The apparent solubility of encapsulated curcumin was in the range 20–51 μg mL−1, that is, three orders of magnitude higher than the water solubility of free curcumin (0.011 μg mL−1). The drug release profiles showed induction periods both at pH levels 4.5 and 7.4, suggesting a diffusive release mechanism, as confirmed by kinetic studies. The release rate of curcumin was higher at pH 7.4 than at pH 4.5 and, in both cases, it was higher for the P5 complex. Encapsulated curcumin was more photostable than the free drug. Molecular mechanics and molecular dynamics simulations explain at atomistic level the formation of aggregates due to favorable van der Waals interactions. The drug molecules interact with the external surface of carriers or form inclusion complexes with the β-cyclodextrin cavities. The aggregate stability is higher at pH 4.5.

Optimization, Characterization, Molecular Docking, and In Vitro Release of BBH/Lysine‐β‐cyclodextrin Inclusion Complex

“…Furthermore, the experimental 13 C NMR result of the Lys-β-CD was shown in Figure 1(C). The peak at 181.66 ppm is the carboxyl carbon peak on Lys, and the peak at 102.28 ppm is the pyran of CD, the peaks at the first carbon position on the ring, 81.06 ppm, 73.03 ppm, 72.05 ppm and 71.77 ppm are respectively Characteristic peaks at 4, 5, 2, and 3 carbon sites in the pyran ring of CD.…”

“…[12] CDs have a conetype cylinder structure consisting of a hydrophobic cavity and a hydrophilic outer surface, which enables them to encapsulate a variety of hydrophobic small molecules through host-guest interactions. [13] β-CD was extensively used due to its suitable cavity size and low price. [14] However, the native β-CD has very low water solubility as well as hemolytic and nephrotoxic effects.…”

“…They are enzymatically derived from starch and are generally considered safe ingredients [12] . CDs have a cone‐type cylinder structure consisting of a hydrophobic cavity and a hydrophilic outer surface, which enables them to encapsulate a variety of hydrophobic small molecules through host‐guest interactions [13] . β‐CD was extensively used due to its suitable cavity size and low price [14] .…”

Adsorption and Self-Aggregation of Chiral [5]-Aza[6]helicenes on DNA Architecture: A Molecular Dynamics Study

“…For about 25 years, personal attention has been paid to atomistic simulations based on MM and MD methods. The possibility of understanding the role of noncovalent intermolecular interactions is interesting, for example, in the adsorption process of proteins on biomaterial surfaces; − in the chiral discrimination in host–guest compounds involving cyclodextrins; and in the nanoaggregation process of carriers and drugs for drug delivery. − These theoretical studies can be useful in explaining experimental data from circular dichroism and two-dimensional NMR spectra when the experimental data are accessible. In some cases, these studies may also be useful in predicting the unfolding state and denaturation of albumin on ordered graphite surfaces, − the solubilization of carbon nanotubes using proteins − or indicating the discrimination of chiral molecules using chiral NTs …”

Different Conformational Properties and Frequencies of Periodic Motion in the β‐ and γ‐Cyclodextrin

“…Other CD derivatives are CD polymers or oligomers, that can be used as building blocks for DOI: 10.1002/masy.202200160 supramolecular structures. [7][8][9][10][11] CDs can be linked covalently or aggregates, thank to non-covalent interactions. [12][13][14] The 𝛼-CD and 𝛽-CD are the most common natural CDs.…”