Characterization of Methylprednisolone Esters of Hyaluronan in Aqueous Solution:  Conformation and Aggregation Behavior

Abstract

Methylprednisolone steroid esters of hyaluronan differing in degree of functionalization and molecular weight were investigated in aqueous solution. Conformation and aggregation phenomena were elucidated by means of circular dichroism, viscometry, rheology, and nuclear magnetic resonance, mainly by (1)H pulsed field gradient (PFG) NMR, which allows the determination of the diffusion coefficient of the species under investigation. The functionalization of hyaluronan with the steroid induces a reduction of the molecular volume, as a consequence of intramolecular hydrophobic interactions. For concentrated samples we have observed the coexistence of unimolecular collapsed chains and of aggregates, the latter disappearing upon dilution. The methylprednisolone ester of lower molecular weight hyaluronan has a larger molecular volume than its higher molecular weight analogue, even though still smaller than the underivatized polymer. This effect can be explained with the reduced flexibility of the polymer backbone probably impairing intramolecular interactions.

Fishing for fire: strategies for biological targeting and criteria for material design in anti‐inflammatory therapies

“… Prodrugs via “conjugation to.” Preformed, reactive macromolecules are derivatized with an active principle at their termini or, most commonly, in their side chains. From a physicochemical point of view, it is important to note that the association of a possibly hydrophobic drug to a hydrophilic polymer may determine aggregation and can be used to produce colloidal carriers in a process that is often referred to as “drug‐induced” self‐assembly, for example, the functionalization of HA with steroidal compounds leads to the formation of micellar structures in water and to the possibility of insertion in lipidic membranes . We refer to the review of Delplace et al .…”

Current research on hyaluronic acid-drug bioconjugates

“…When the HA-MPL conjugate was incubated in buffer solution under different pH conditions, the drug release amount was gradually increased along with the rising pH varying from 6.5 to 8.0 [81]. This release also accelerated along with the temperature rising from 20 C to 37 C. The aggregation behavior of HA-MPL conjugate was further assessed in aqueous solution [82]. Probably owing to hydrogen bond network being destroyed to some extent, high substitution degree of MPL in the conjugate resulted in low viscosity.…”

Investigating the Interactions of Hyaluronan Derivatives with Biomolecules. The Use of Diffusional NMR Techniques

“…For reasons discussed in detail in a previous paper, [39] we have chosen to follow the peak at d ¼ 1.95 ppm, which corresponds to the acetamido group of HA. All samples were measured in distilled H 2 O, used for the reconstitution of the powders, with the addition of variable amounts of D 2 O in order to obtain the desired concentration and using 0.025 M NaOH as titrant when adjusting pH to 7.0 was required.…”

“…carboxyl groups in HYCp45 and HYCp60, respectively), and we have compared their behavior with that of native HA. These macromolecules can be seen as self-associating drug carriers, [39] since methylprednisolone is a steroidal anti-inflammatory drug and can be released by the hydrolysis of the ester linkage between HA carboxyl group and the hydroxyl group in C-21 position; however, they can also be used as a generic model for any self-assembled colloidal structures which display HA on the surface (Scheme 2).…”