Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for Ocular Drug Delivery

Abstract

Many studies have focused on how drugs are formulated in the sol state at room temperature leading to the formation of in situ gel at eye temperature to provide a controlled drug release. Stimuli-responsive block copolymer hydrogels possess several advantages including uncomplicated drug formulation and ease of application, no organic solvent, protective environment for drugs, site-specificity, prolonged and localized drug delivery, lower systemic toxicity, and capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling block copolymers (such as diblock, triblock, and pentablock copolymers) with large solubility variation between hydrophilic and hydrophobic segments are capable of making temperature-dependent micellar assembles, and with further increase in the temperature, of jellifying due to micellar aggregation. In general, molecular weight, hydrophobicity, and block arrangement have a significant effect on polymer crystallinity, micelle size, and in vitro drug release profile. The limitations of creature triblock copolymers as initial burst release can be largely avoided using micelles made of pentablock copolymers. Moreover, formulations based on pentablock copolymers can sustain drug release for a longer time. The present study aims to provide a concise overview of the initial and recent progresses in the design of hydrogel-based ocular drug delivery systems.

Novel nano-vehicle for delivery and efficiency of anticancer auraptene against colon cancer cells

“…In formulation type II and III by increasing of polymer to drug ratio the differences between TB and PB were not remarkable in terms of entrapment efficiency and loading capacity. As other studies reported that drug loading capacity and entrapment efficiency of NPs are mostly depended on copolymer compositions in which drug entrapment can be enhanced by increasing the molecular weight of lipophilic part of copolymers 22,24 .…”

“…We found that the differences between release profiles of each of NPs depended on physiochemical characteristics such as NPs sensitivity to temperature, solubility, crystallinity, molecular weight and rate of degradation. Previous studies reported that these synthesized copolymers (PCL-PEG-PCL and PLA-PCL-PEG-PCL-PLA) are thermosensitive hydrogels and pentablock copolymer indicates better solubility, lower crystallinity and faster degradation compared to triblock copolymer due to the presence of PLA blocks which directly affected drug release profile 22,24,41 .…”

“…In our study, the IC 50 value of free AUR, AUR loaded TB and AUR loaded PB on HT-29 cells which were obtained by MTT assay were 13.05, 31.9 and 10.1 µg.ml −1 , respectively. Based on the results achieved from MTT assay, in terms of optimal dose and exposure time, the experiments were carried out in two 15 µg.mL −1 (IC 50 of AUR) and 7.5 µg.mL −1 (sub IC 50 dose) for 72 h. After 48 h exposure of HT-29 cells to mentioned treatment groups, cell mortality rate in free AUR was higher than AUR loaded TB and AUR loaded PB due to the slow release of drug from micelles 22 . But over 72 h incubation, AUR loaded PB showed superior cell cytotoxic effects compared to AUR loaded TB and free AUR.…”

“…Furthermore because of lipophilic nature, this polymer is able to entrap hydrophobic drugs through hydrophobic interactions 21 . PCL-PEG-PCL(triblock, TB) and PLA-PCL-PEG-PCL-PLA (pentablock, PB) copolymers have significant properties, such as long-term targeted drug delivery and ability to carry both hydrophobic and hydrophilic drugs 22 . These polymers can form micellar structures with an internal hydrophobic surface and an external hydrophilic surface in the aqueous solutions and the heart of the micellar structure can act as a reservoir for compounds with very low solubility in water.…”

A novel thermo-sensitive hydrogel-based on poly(N-isopropylacrylamide)/hyaluronic acid of ketoconazole for ophthalmic delivery

“…Ophthalmic delivery is one of the most challenging tasks for pharmaceutical practitioners [1]. The unique structure of the eye restricts the entry of drug molecules into the desired site.…”