Long‐Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment Using a Microspheres/Carrier System

Pek, Y. Shona; Wu, Hanshuo; Mohamed, Siti Thaharah; Ying, Jackie Y.

doi:10.1002/adhm.201600780

Cited by 20 publications

(13 citation statements)

References 41 publications

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“…PLLA is generally considered as a biocompatible and biodegradable polymer used in many biomedical applications including scaffolds for tissue engineering and vehicles for drug delivery. [11c,20] A low residual content of organic solvent dichloromethane reported in our previous study could further improve the safety of PLLA PMs comparing to other conventional fabrication technologies . Indeed, the results in Figure a demonstrated that the relative viable cell counts were all higher than 90% in the negative control (no treatment) and various treatment groups (0.25–1.00 mg mL −1 ) at different exposure times, while those dropped to 10% or lower in the positive control group (phenol treatment), suggesting the cytocompatibility of the PLLA PMs.…”

mentioning

confidence: 71%

“…Polymers are highly advantageous as carriers for inhalation delivery because of their ability to carry a high payload of drugs, easy drug impregnation, biocompatibility, biodegradability, and sustainability of drug/protein release from the matrix, among others. Poly‐ l ‐lactide (PLLA) is one such polymer with the aforementioned qualities and has been utilized for various biomedical applications such as drug delivery, tissue engineering, and others …”

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confidence: 99%

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Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Lin

Kankala

Tang

et al. 2018

Adv Healthcare Materials

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Pulmonary delivery of therapeutic agents has attracted increasing attention in biomedicine, as the lung is suitable to absorb large amounts of drugs due to its unique physiological characteristics, such as the high surface area (≈100 m 2 ), receipt of the entire cardiac output, thin blood-alveolar barrier, and low enzyme activity, among others. [1] In a way, insulin (INS) delivery through inhalation has been effective and well-tolerated, and provides significant glycemic control compared to the conventional, frequently administered, and invasive subcutaneous regimens. For example, Exubera was the first dry powder-based inhalation formulation of INS approved by the Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO 2 ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) by using the SC-CO 2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung-derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α, compared with the negative control group. INS-PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS-PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes. Insulin Delivery

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confidence: 71%

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confidence: 99%

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Lin

Kankala

Tang

et al. 2018

Adv Healthcare Materials

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“…Many formulations have been developed to circumvent these problems related to the treatment with eye drops. Examples of such systems are contact lenses (Peng et al, 2012), liposomes (Abu Hashim, El‐Dahan, Yusif, Abd‐Elgawad, & Arima, 2014; Pisal, Joshi, Padamwar, Patil, & Pokharkar, 2014), microspheres (Pek, Wu, Mohamed, & Ying, 2016) and solid inserts (Shivakumar, Desai, Subhash, Ashok, & Hulakoti, 2007).…”

Section: Introductionmentioning

confidence: 99%

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study

Cesar

Navarro

Castilho

et al. 2020

J Biomedical Materials Res

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A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open‐angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

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“…Certain drugs harness the differing lipophilicity of the cornea to their advantage for drug delivery. Latanoprost is one of the most common ocular drugs used for the treatment of glaucoma, a disease in which there is accelerated optic nerve degeneration in association with a raised IOP (Digiuni et al, ; Pek et al, ). Latanoprost is a prostaglandin analogue that reduces IOP by increasing the uveoscleral outflow, through targeting receptors near the drainage angle.…”

Section: Introductionmentioning

confidence: 99%

Principles of pharmacology in the eye

Awwad

Mohamed-Ahmed

Sharma

et al. 2017

British J Pharmacology

163

138

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*These authors contributed equally to this work.The eye is a highly specialized organ that is subject to a huge range of pathology. Both local and systemic disease may affect different anatomical regions of the eye. The least invasive routes for ocular drug administration are topical (e.g. eye drops) and systemic (e.g. tablets) formulations. Barriers that subserve as protection against pathogen entry also restrict drug permeation. Topically administered drugs often display limited bioavailability due to many physical and biochemical barriers including the precorneal tear film, the structure and biophysiological properties of the cornea, the limited volume that can be accommodated by the cul-de-sac, the lacrimal drainage system and reflex tearing. The tissue layers of the cornea and conjunctiva are further key factors that act to restrict drug delivery. Using carriers that enhance viscosity or bind to the ocular surface increases bioavailability. Matching the pH and polarity of drug molecules to the tissue layers allows greater penetration. Drug delivery to the posterior segment is a greater challenge and, currently, the standard route is via intravitreal injection, notwithstanding the risks of endophthalmitis and retinal detachment with frequent injections. Intraocular implants that allow sustained drug release are at different stages of development. Novel exciting therapeutic approaches include methods for promoting transscleral delivery, sustained release devices, nanotechnology and gene therapy.

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Long‐Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment Using a Microspheres/Carrier System

Cited by 20 publications

References 41 publications

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study

Principles of pharmacology in the eye

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