Effect of hydrophobic and hydrophilic additives on sol-gel transition and release behavior of timolol maleate from polycaprolactone-based hydrogel

Abstract

The objective of this work was to delineate the effect of hydrophilic and hydrophobic polymeric additives on sol-gel transition and release profile of timolol maleate (TM) from poly (ethylene glycol)-poly (ε-caprolactone)- poly (ethylene glycol) (PEG-PCL-PEG)-based thermosensitive hydrogel. Polycaprolactone (hydrophobic additive) and polyvinyl alcohol (PVA) (hydrophilic additive) reduced critical gel concentration of PEG-PCL-PEG triblock polymer. The effect of PCL on sol-gel transition was more pronounced than PVA. However, with PCL no statistically significant difference in release profile was observed. The effect of PVA on release profile was more pronounced, which reduced the cumulative percentage release of TM from 86.4±0.8% to 73.7±1.8% over 316 h. Moreover, cytotoxicity of the hydrogel was also investigated utilizing rabbit primary corneal epithelial culture cells. No significant cytotoxicity of hydrogel alone or in presence of additives was observed. So, polymeric additive strategy serves as a valuable tool for optimizing TM release kinetics from PEG-PCL-PEG hydrogel matrix.

Fig. 1. Synthetic scheme of PEG–PCL–PEG

Fig. 2. ¹H-NMR spectra of PECE copolymer in CDCl₃

Fig. 3. Gel permeation chromatogram of PCEC II

Fig. 4. FTIR spectrum of PEG–PCL–PEG

Fig. 5

Sol–gel transition phase diagram. a PCEC II triblock copolymer aqueous solutions alone and with 5 wt.% PVA; b PCEC II triblock copolymer aqueous solutions alone and with 5 wt.% PCL

Fig. 6

Photograph of PCEC II at 25 °C a alone, b with 5 wt.% PVA, and c with 5 wt.% PCL and at 37 °C d alone, e with 5 wt.% PVA, and f with 5 wt.% PCL

Fig. 7

SEM of PCEC II a alone, b with 5 wt.% PCL, c with 5 wt.% PVA

Fig. 8

Effect of molecular weight and drug loading. a release of TM from PCEC I and PCEC II triblock copolymer (25 wt. %) hydrogel; b release of TM 0.5 and 1.0 wt.% from PCEC II triblock copolymer (25 wt.%) hydrogel in PBS buffer (pH 7.4) at 37 °C. The values are represented as mean ± standard deviation of n=3

Fig. 9

Effect of polymeric additives. a release of TM from PCEC II (25 wt.%) and PCEC II (20 wt.%) with 5 wt.% PVA ; b release of TM from PCEC II (25 wt.%) and PCEC II (20 wt.%) with 5 wt.% PCL hydrogel in PBS buffer (pH 7.4) at 37 °C. The values are represented as mean ± standard deviation of n=3

Fig. 10

Rabbit primary corneal epithelial culture cell viability study. Cell survival decreased with increase of concentration of PECE hydrogel. The values are represented as mean ± standard deviation of n=6