DRUG DELIVERY
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2022
·
IF 6.819
Yujin Zhao,Chang Huang,Zhutian Zhang,Jiaxu Hong,Jianjiang Xu,Xinghuai Sun,Jianguo Sun
Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit’s conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.
研究领域:
药剂学
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眼科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Expert Opinion on Drug Delivery
·
2024
·
IF 5
Zhutian Zhang,Qian Ma,Zhaoxing Dai,Jiaxu Hong,Jifeng Gu,Rong Shi,Jianjiang Xu,Yaling Ma,Xinghuai Sun,Jianguo Sun
Background Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance.Methods A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed.Results The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion.Conclusions The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.
研究领域:
药剂学
·
眼科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Huamei Li,Fuda Dai,Hanyu Liu,Qi Tao,Jie Hu,Yangrong Zhang,Zhenping Xiao,Ilva D. Rupenthal,Huihui Li,Fan Yang,Wei Li,Huaqing Lin,Dongzhi Hou
Recently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.
研究领域:
药剂学
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眼科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Jing Li,Lin Wu,Weijun Wu,Baoyan Wang,Zhongyuan Wang,Hongliang Xin,Qunwei Xu
Poor corneal penetration and short preocular retention of a clinical hydrophilic drug, pilocarpine nitrate (PN), for the treatment of open-angle glaucoma and acute angle-closure glaucoma, limit its ocular application. The purpose of this study was to investigate the potential of liquid crystal nanoparticles (LCNPs) for ocular delivery of PN. LCNPs were developed by a top-down method using glyceryl monoolein (GMO) and water in the presence of stabilizer Poloxamer 407 . They were characterized by transmission electron microscopy (TEM) and small angle X-ray diffraction (SAXS). The size of LCNP is 202.28 ± 19.32 nm and the encapsulation efficiency reached 61.03%. The in vitro release profiles indicated that PN could keep sustained release from PN-loaded LCNPs for 8 h. An ex vivo corneal permeation study revealed that the apparent permeability coefficient of PN-loaded LCNPs was 2.05-fold higher than that of commercial eye drops. In addition, the topical administration test showed that PN-loaded LCNPs had a prolonged effect on decreasing intraocular pressure (IOP) of rabbits compared with commercial drug and physiological saline. In conclusion, LCNPs had been demonstrated to be potential for controlled-release ocular drug delivery.
研究领域:
药剂学
·
眼科医学
✓ 已验证
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Tao Wang,Yunran Zhang,Meiling Chi,Chen Zhao,Linlin Cao,Chutong Tian,K. Kamei,Ying Zheng,Qikun Jiang
Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration, poor efficacy and side effects. Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution (FC-TNL) has the ability to treat glaucoma by lowering the intraocular pressure (IOP) with great efficacy and improving patient compliance. However, the commercialized netarsudil dimesylate precipitated when the pH of the solution was above 5.4, or when maleic acid, the salt of commercial timolol maleate, was mixed with netarsudil dimesylate. Consequently, the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in pH 4.8–5.2 solution by synthesizing timolol mesylate. Next, the morphology of timolol mesylate was observed by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction. The prepared FC-TNL showed good stability during refrigeration storage. Additionally, FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study. Importantly, once-daily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells. The FC-TNL was stable, safe and effective, being a promising glaucoma therapeutic.
研究领域:
药理学
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眼科医学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2023
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IF 4.9
Jingyi Zhao,Jian Xiong,Yun Ning,Jiansong Zhao,Zhipeng Wang,Linhui Long,Haibing He,Jingxing Gou,Tian Yin,Xing Tang,Yu Zhang
Glaucoma is a chronic disease that requires lifelong treatment, whereas, discomfort caused by frequent medication may affect the quality of life. Moreover, the therapeutic efficacy of traditional local administration was unsatisfactory due to the rapid ocular clearance mechanism and the ocular barrier. Herein, a triple crosslinked micelle-hydrogel lacrimal implant with low polymer content was fabricated for localized and prolonged therapy of glaucoma. Latanoprost and timolol were simultaneously entrapped in the PEG-PLA micelles with high encapsulation efficiency and further loaded into the triple crosslinked hydrogel, facilitating a double sustained release of drugs. Subsequently, the implant was constructed by a unique molecular orientation fixation technology, which enables the implant to be fixed in the lacrimal duct. The triple crosslinked micelle-hydrogel lacrimal implant manifested a distinguished physicochemical characterization to sustain the release of latanoprost and timolol. In vitro release experiment demonstrated the duration of two drugs was extended for up to 28 days. The in vivo test of elevated intraocular pressure (IOP) in a rabbit model revealed that the IOP-lowering effects were sustained longer than 28 days as expected. The relative pharmacological availability (PA) of lacrimal implants was 5.7 times greater than that of the eye drops. The results of the studies on ocular irritation and histological examination demonstrated the good safety of the lacrimal implant. In conclusion, the triple crosslinked micelle-hydrogel lacrimal implant could effectively lower the IOP with splendid compatibility, demonstrating the promising prospect in the long-term noninvasive treatment of glaucoma.
研究领域:
药剂学
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眼科医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Ophthalmology
·
2020
·Vol. 20
·期 1
·1-7
·
IF 1.413
Yu A-Yong,Shao Hui,Pan Anpeng,Wang Qinmei,Huang Zixu,Song Benhao,McAlinden Colm,Huang Jinhai,Chen Sisi
Background To investigate the biomechanical properties of the cornea in myopic eyes using corneal visualization Scheimpflug technology (Corvis ST). The relationships between the biomechanical properties of the cornea and the degree of myopia were also investigated. Methods 265 eyes of 265 subjects were included. Based on spherical equivalent (SE) in diopters (D), participants were divided into four groups: low myopia/control (SE: − 0.50 to − 3.00D), moderate myopia (SE: − 3.00 to − 6.00D), high myopia (SE: − 6.00 to − 10.00D) and severe myopia (SE greater than − 10.00D). Axial length (AL), anterior segment parameters, and corneal biomechanical properties were obtained with the Lenstar LS900, Pentacam HR and Corvis ST, respectively. Results Mean (±SD) SE was − 7.29 ± 4.31D (range: − 0.63 to − 25.75D). Mean AL was 26.31 ± 1.82 mm (range: 21.87 to 31.94 mm). Significant differences were detected within the four groups in terms of six corneal biomechanical parameters: deformation amplitude (DA), time from start until second applanation (A2-time), length of flattened cornea at the second applanation (A2-length), corneal velocity during the first and second applanation (A2-velocity), time from start to highest concavity (HC-time), and central curvature at highest concavity (HC radius). AL was positively associated with DA whereas negatively associated with A1-velocity and A2-length. SE was positively associated with A2-time, HC-time and A2-velocity, whereas negatively associated with DA. IOP was positively associated with four corneal biomechanical parameters and negatively associated with three parameters. Conclusions Eyes with severe myopia showed greater DA, lesser A2 time, HC time, and faster A2-velocity compared to low to high myopia. This suggests the cornea becomes weaker and more deformable with elongation of axial length with corresponding increases in myopia. DA, A2-time and A2-velocity could be useful corneal biomechanical indicators in patients with myopia.
研究领域:
眼科
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视觉科学
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生物力学
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屈光医学
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医学影像学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）