Generation 5 (G5) poly(amidoamine) dendrimers with acetyl (G5.NHAc), glycidol hydroxyl (G5.NGlyOH), and succinamic acid (G5.SAH) terminal groups were used to physically encapsulate an anticancer drug doxorubicin (DOX). Both UV-vis spectroscopy and multiple NMR techniques including one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between different dendrimers and DOX. The influence of the surface functional groups of G5 dendrimers on the DOX encapsulation, release kinetics, and cancer cell inhibition effect was investigated. We show that all three types of dendrimers are able to effectively encapsulate DOX and display therapeutic inhibition effect to cancer cells, which is solely associated with the loaded DOX. The relatively stronger interactions of G5.NHAc or G5.NGlyOH dendrimers with DOX than that of G5.SAH dendrimers with DOX demonstrated by NMR techniques correlate well with the slow release rate of DOX from G5.NHAc/DOX or G5.NGlyOH/DOX complexes. In contrast, the demonstrated weak interaction between G5.SAH and DOX causes a fast release of DOX, suggesting that the G5.SAH/DOX complex may not be a proper option for further in vivo research. Our findings suggest that the dendrimer surface functional groups are crucial for further design of multifunctional dendrimer-based drug delivery systems for various biomedical applications.
Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels.
Medium generation PAMAM dendrimers are extensively researched as drug delivery vehicles therefore detailed knowledge of their physico-chemical properties in solution is vital. We have selected ethylenediamine core, generation five poly(amidoamine) (PAMAM_E5) dendrimers (amine terminated PAMAM_E5.NH 2 and its succinamic acid derivative PAMAM_E5.SAH, respectively) as model compounds to study their dynamic behavior in water as a function of pH and concentration. Diffusion coefficients of water and the dendrimers were determined in deuterium oxide using pulse-field gradient stimulated echo (PGSE) NMR. The diffusion rate for PAMAM_E5.NH 2 increased monotonously with increasing pH values while for PAMAM_E5.SAH a maximum was found at an isoelectric value of pH ¼ 5.7. The apparent diffusion coefficients of dendrimers decreased linearly with increasing concentration measured at their self-pH (pH ¼ 9.4 for PAMAM_E5.NH 2 and pH ¼ 5.7 for PAMAM_E5.SAH) in the absence of added salts. The observations could be explained by considering hard sphere interactions between strongly hydrated dendrimer molecules. The average hydrodynamic radii of dendrimers were determined by extrapolating the measured diffusion coefficients to zero dendrimer concentration and applying the Stokes-Einstein equation. The calculated values were R H ¼ 3.05 AE 0.04 nm for PAMAM_E5.NH 2 and R H ¼ 3.37 AE 0.08 nm for PAMAM_E5.SAH respectively. Measured diffusion coefficients of water (D 2 O) also decreased linearly with increasing dendrimer concentration. From the concentration dependence, the average number of water molecules that form one dynamic unit with one macromolecule could be calculated on the basis of three different obstruction models. It has been concluded that hydrated PAMAM dendrimers in aqueous solutions behave as soft colloids against solvent molecules but as hard-sphere colloids against each other. Their equivalent hard-sphere radii were found to be equal to the measured hydrodynamic radii.
Abstract. Mesoporous silica aerogel particles of ca. 5 µm in diameter can be conveniently produced by grinding in aqueous phosphate buffer at pH 7. The pores in the suspended aerogel particles are spherical and their diameter is 18 -20 nm, as measured by NMR cryoporometry.NMR diffusiometry revealed that diffusion of water is hindered inside the pores of the aerogel. In spite of steric hindrance, bulk water and pore water exchange rapidly on the millisecond timescale in the suspension, indicating a highly interconnected pore network. The adsorption of methylene blue (MB), as a model compound, was studied on the silica aerogel particles. The process was followed by on-line UV-Vis spectrophotometry after injecting the dye into the aerogel suspension. Biphasic kinetics was observed with the first process complete in ca. 80 s and the second in ca. 600 s. A detailed kinetic model was developed for the interpretation of the results. It postulates a relatively fast adsorption process with Langmuir-type kinetics, and the aggregation of aerogel particles covered by the dye on the longer timescale. The aggregates are involved in a reversible sedimentation process which actually remove MB from the suspension.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.