Hydrogels of Poly(2-hydroxyethyl methacrylate) and Poly(N,N-dimethylacrylamide) Interpenetrating Polymer Networks as Dermal Delivery Systems for Dexamethasone

Abstract

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G' values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN's composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9-1), depending on the IPN's composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells.

Keywords: CCL-1; HUT-78; dermal application; dexamethasone; drug delivery; hydrogels; interpenetrating polymer networks; non-cytotoxic.

Figure 1

Storage modulus (G′) (full symbols) and loss modulus (G″) (empty symbols) for the straight PDMAM/PHEMA IPNs (A) and for the reverse PHEMA/PDMAM IPNs (B) obtained via frequency sweep experiments.

Figure 2

Mesh sizes (ξ) of (A) PDMAM/PHEMA IPN and (B) PHEMA/PDMAM IPN hydrogels as a function of PDMAM content.

Figure 3

ESR for PDMAM/PHEMA IPNs synthesized using PDMAM SNs with 0.1 mol.% PEGDA in water and in ethanol (EtOH) (A) and ESR for PHEMA/PDMAM IPNs in EtOH (B).

Figure 4

ESR of PDMAM SN with 0.4 mol.% PEGDA (D04) and its IPN with PHEMA (D04H500), in water and in ethanol (EtOH).

Figure 5

SEM images of fractured surfaces of PDMAM SNs and PDMAM/PHEMA IPNs. Red arrows point at the second phase domains of PHEMA.

Figure 6

Dependence of DEX EE (A) and DL (B) in PHEMA SN and PHEMA/PDMAM IPNs as a function of their composition (${\mathrm{r}}_{\mathrm{D}}^{\mathrm{r}}$).

Figure 7

Dependence of DEX EE (A) and DL (B) in PDMAM SNs and PDMAM/PHEMA IPNs, synthesized using PDMAM SNs with 0.1 mol.% PEGDA as a function of their composition (${\mathrm{r}}_{\mathrm{D}}^{\mathrm{s}}$).

Figure 8

Drug release profiles of DEX from PHEMA SN (H1) and PHEMA/PDMAM IPNs (H250 and H500) (A) and from PDMAM SN (D01) and PDMAM/PHEMA IPNs (D01H125 and D01H500) (B).

Figure 9

Cell viability of cutaneous T-cell lymphoma cells (HUT-78) and normal murine fibroblast cell line (CCL-1) following 72 h exposure to different concentrations of H1 and H500 PHEMA/PDMAM IPNs. All experiments were run in triplicate and data are expressed as the mean ± SD. Statistical significance of the data was assessed using a one-way ANOVA (p-value ≤ 0.05 was considered statistically significant).