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

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

Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for ocular delivery of dexamethasone

Objective(s): Micelles have been studied as nanoparticulate drug delivery systems for improving the topical ocular delivery of hydrophobic drugs. The objective of this study was to develop and characterize dexamethasone-loaded polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient compliance and enhance the ocular bioavailability of poorly water-soluble drugs. Materials and Methods: The PCL-PEG-PCL copolymers were synthesized via the ring opening polymerization of ε-caprolactone in the presence of PEG. The resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC. The critical micelle concentrations (CMCs) of the copolymers mentioned were determined. Dexamethasone was loaded into polymeric micelles by film hydration method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug release kinetics and ex vivo corneal permeability were also determined. Results: The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at 34 °C. The TEM results exhibited the successful formation of spherical micelles. The size of the prepared micelles was approximately 40 nm. Formulated micelles sustained the release of the incorporated dexamethasone for 5 days. Conclusion: Data from ex vivo permeability tests indicated that PCL-PEG-PCL micelles can be suitable candidates for the ocular delivery of dexamethasone and, likely, other hydrophobic drugs

Fast Dissolving Sublingual Films Containing Sumatriptan Alone and Combined with Methoclopramide: Evaluation in Vitro Drug Release and Mucosal Permeation

ackground: Sumatriptan succinate is a 5-HT1 receptor agonist which is used in the treatment of migraine. It shows low bioavailability (15%) due to high hepatic first pass metabolism. The present work intended to formulate mucoadhesive sublingual films of sumatriptan combined with metoclopramide and sumatriptan alone with the objective of improving the therapeutic efficacy, patient compliance, and bioavailability. Methods: The sublingual films were formulated by solvent casting technique using mucoadhesive polymer of hydroxypropyl methylcellulose and propylene glycol as plasticizers. This study was also designed to evaluate the physicochemical and mucoadhesive characteristics of the films. The films were evaluated for their mechanical strength, folding endurance, drug content uniformity, swelling, in vitro residence time, in vitro release, in vitro bioadhesion, and in vivo mucoadhesion. Results: They showed good appearance and elasticity. The best drugs of polymer ratio were S3 (1:2) and SM2 (2.7:1:8). The film of S3 and SM2 showed 10.6 and 11.01 mg weight, 2.2 and 22.5 µm thickness, 300 folding endurance, 55.9 and 100% content uniformity, respectively. The Differential Scanning Calorimetry (DSC) showed no stable sample of sumatriptan and metoclopramide in the drug loaded films and revealed amorphous form and transition of hydrate to anhydrous form for metoclopramide. The results showed that the films prepared were fast dissolving. The films (sumatriptan combined with metoclopramide and sumatriptan alone) exhibited very good mucoadhesive properties and shorter retention time (15-30 s). Conclusion: The formulations were found to be suitable candidates for the development of sublingual films for therapeutic uses