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

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

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

Montmorillonite-loaded solid lipid nanoparticles with good biocompatibility, using Betaxolol hydrochloride as model drug, were prepared by the melt-emulsion sonication and low temperature-solidification methods and drug bioavailability was significantly improved in this paper for the first time to application to the eye. The appropriate physical characteristics were showed, such as the mean particle size, Zeta potential, osmotic pressure, pH values, entrapping efficiency (EE%) and drug content (DC%), all showed well suited for possible ocular application. In vitro release experiment indicated that this novel system could continuously release 57.83% drugs within 12 h owing to the dual drug controlled-release effect that was achieved by ion-exchange feature of montmorillonite and structure of solid lipid nanoparticles. Low irritability and good compatibility of nanoparticles were proved by both CAM-TBS test and cytotoxicity experiment. We first discovered from the results of Rose Bengal experiment that the hydrophilicity of the drug-loaded nanoparticles surface was increased during the loading and releasing of the hydrophilic drug, which could contribute to prolong the ocular surface retention time of drug in the biological interface membrane of tear-film/cornea. The results of in vivo pharmacokinetic and pharmacodynamics studies further confirmed that increased hydrophilicity of nanoparticles surface help to improve the bioavailability of the drug and reduce intraocular pressure during administration. The results suggested this novel drug delivery system could be potentially used as an in situ drug controlled-release system for ophthalmic delivery to enhance the bioavailability and efficacy

Dual controlled release effect of montmorillonite loaded polymer nanoparticles for ophthalmic drug delivery

Montmorillonite based polymeric nanoparticles was designed to effectively deliver adequate concentrations of drug to the ocular site after topical administration for treatment of glaucoma. In vitro and in vivo studies were carried out to evaluate their drug delivery performances. Betaxolol hydrochloride (BH) intercalated montmorillonite (Mt-BH) was successfully encapsulated into the Eudragit (R) PO (Mt-BH NPs) via an opportunely emulsification-solvent evaporation technique as indicated by Fourier transform infrared, differential scanning calorimentry, and the nitrogen sorption and desorption isotherms. The resulting nanoparticle system showed the mean particle diameters of 82 +/- 8 nm and positive. potentials, with encapsulation efficiency of 77 +/- 1% and drug-loading rate of 8 +/- 2%. Interestingly, in vitro release profile of Mt-BH NPs exhibits an initial burst of surface-bound BH, followed by a slow release of BH due to polymer erosion, and a further drug release after the particle completely breakdown. About 80% were released after 10 h. The designed drug delivery system showed little irritation and well tolerance of nanoparticles in a chorioallantoic membrane assay. The new Eudragit (R) PO polymer nanoparticles system reported here is expected to be useful in ophthalmic application