Injectable Maltodextrin-Based Micelle/Hydrogel Composites for Simvastatin-Controlled Release

Abstract

Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.

Long‐Term Controlled Release of Simvastatin from Photoprinted Triple‐Networked Hydrogels Composed of Modified Chitosan and PLA–PEG Micelles

“…For previously reported in vitro release studies, the loading amount of statin drugs per scaffold varies widely from 0.4 µg mL −1 to 10 mg mL −1 . [ 27–36 ] Regardless of the loading concentration, the reported SMV release from hydrogel scaffolds was much smaller amount and lasted shorter period compared to our results. For example, Yan et al.…”

“…[ 30 ] Some other studies loaded SMV in various hydrogels with 1–3 mg mL −1 concentrations (similar to our study), but drug release tests were carried in very small‐scale with diluted conditions and resulted only 0.4–1.0 µg of cumulative SMV release which completed within 30 days. [ 29,32 ] Although it is difficult to translate these results for the necessary dose of SMV in vivo, reported small animal studies indicated that 2–10 and 100–200 mg of SMV per scaffold seem to be effective concentrations in promoting bone regeneration for small and large bone defect models, respectively. [ 26 ] The extended delivery result in our large‐scale drug release study demonstrated feasibility of the hydrogel regeneration system.…”

“…encapsulated SMV in chemically modified C16‐maltodextrin micelles, then embedded the micelles in chitosan/maltodextrin hydrogels with Schiff base cross‐linking. [ 29 ] They observed a huge burst of SMV release in 1 day from non‐cross‐linked micelles in the hydrogel. By contrast, direct loading of SMV in the hydrogel matrix showed a slow and low amount of cumulative release with equilibrium in 10 days.…”

Bio-based composite hydrogels for biomedical applications

“…Yan et al prepared micelle/hydrogel composites for the controlled release of simvastatin to achieve local bone regeneration ( Figure 1). 52 Composites of polymeric micro-or nanoparticles embedded in hydrogels may also facilitate the simultaneous delivery of multiple drugs with different solubility. This is important to enable combination therapy, which has shown several advantages compared to monotherapy such as reduced side effects 56 and lowering of drug resistance.…”

Poly(l‐glutamic acid)‐based micellar hydrogel with improved mechanical performance and proteins loading

“…Among these efforts, introduction of micelles, which undergo microscopic phase separation in aqueous environment, could consume the external loading to impart the hydrogels with higher resistance under big strain . Most importantly, the micelles also can work as carriers of biomolecules to realize controlled release, so to improve regeneration effect …”