Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

Abstract

Background Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma.

Advances and limitations of drug delivery systems formulated as eye drops

“…anti-glaucoma drugs (betaxolol [85], acetozalamide [86], brimonidine [87]), amphotericin B [88] and azelastine [89]. Recently, researchers developed a particularly interesting formulation based [124].…”

“…In vitro studies showed an extended release duration of 12h with Eudragit ® /Mt microspheres in comparison to standard betaxolol solution (2.5h) and only Eudragit ® microspheres (5h). Moreover, in vivo Draize rabbit eye test demonstrated a lower toxicity of betaxolol loaded in Eudragit ® /Mt microspheres compared to betaxolol in standard solution[85].…”

Incorporation of ion exchange functionalized-montmorillonite into solid lipid nanoparticles with low irritation enhances drug bioavailability for glaucoma treatment

“…The animals were randomly divided into two groups, the BH group and the Mt-BH-SLNs group, to evaluate the effect of lowering IOP of formulations. After anesthesia, acute high intraocular pressure models were induced by intraperitoneal injection of saline (Tian et al, 2018). The IOP of every modeled eye was determined instantly as the initial IOP when the animals woke up.…”

Influence of new treatment modalities on adherence in glaucoma

“…Other means of application, which rely on less patient adherence, would be preferable, because we know that glaucoma patients are especially not very successful in applying drops [22]. Another alternative way of delivering a drug is via microspheres, a method which has been examined by Tian et al [23]. These microspheres' goal is to prolong the duration of action of the drugs, thus enabling less frequent use.…”