INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Lu Jin,Xiumin Li,Xu Chen,Xinghao Chen,Ye Liu,Haonan Xu,Qiao Wang,Zhan Tang
Puerarin (PUE), an isoflavonoid isolated from Pueraria lobata (Willd) Ohwi root, is a β -adrenergic receptor inhibitor used in treating glaucoma. The concentration range of gellan gum was determined based on the formulation viscosity and gelling capacity. PVP-K30 and gellan gum were used as variables, with the viscosity of formulation: STF = 40: 21, the 4 h permeation rate of rabbit isolated sclera, and 2 h in vitro release rate as response values. The JMP software was used to optimize the results, presenting that gellan gum was the main factor influencing viscosity. The in vitro release and permeation rate were primarily influenced by PVP-K30. The optimal prescription was 0.45% gellan gum and 6.0% PVP-K30. The in vitro release and permeation characteristics of puerarin in situ gel (PUE-ISG) were investigated using PUE solution as a control. The dialysis bag method results indicated that the release of the solution group leveled off after 4 h, while the PUE-ISG group had been continuously releasing. However, the cumulative release rates of the two were no longer significantly different at 10 h. The cumulative permeation rates of the ISG and solution groups were not significantly different ( P > 0.05) in the rabbit isolated sclera. The apparent permeability Papp and steady-state flux Jss of PUE-ISG were 0.950 ± 0.059 cm/h and 9.504 ± 0.587 mg·(cm·h), respectively. A sensitive and stable HPLC-MS/MS analytical method for quantifying aqueous humor concentrations of PUE was validated. A microdialysis technique was successfully used in the aqueous humor pharmacokinetics study to sample aqueous humor from rabbit eye continuously. The results revealed that PUE-ISG significantly increased the drug concentration in the aqueous humor, with C max and AUC (0-t) 3.77 and 4.40 times higher than those of the solution group, respectively. T max was also significantly prolonged, indicating good prospects for clinical application. The developed PUE-ISG preparation has the characteristics of rapid drug release and sustained permeation, and increase the drug concentration in aqueous humor, with all inactive ingredients remaining within the maximum allowable limits recommended by the FDA guideline.
研究领域:
药剂学
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药物代谢动力学
·
眼科
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2022
·
IF 3.318
Jingjing Yang,Zhen Liang,Ping Lu,Fei Song,Zhen Zhang,Huiyun Xia,Jijun He,Tianyang Zhou,Junjie Zhang
Luliconazole (LCZ) is a novel antifungal imidazole with broad-spectrum and high susceptibility of Aspergillus and Fusarium are the dominant species of fungal keratitis, may potentially be a new medical treatment option for ocular fungal infection. To evaluate LCZ distribution in ocular tissues after topical application for the development of ophthalmic delivery system, it is important to have a bioanalytical method for measuring the drug concentrations in different ocular tissues and aqueous humor (AH). A selective and sensitive ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantification of LCZ in rabbit ocular tissues, including conjunctiva, cornea, AH, iris, lens, vitreous humor (VH), retinal choroid and sclera, using lanoconazole as internal standard (IS). Chromatographic separation was achieved on a Xterra MS, C18 column (2.1 × 50 mm, 3.5 μm) using mobile phase with formic acid solution (0.2%, v/v): acetonitrile (50:50, v/v) at a flow rate of 0.2 ml/min, and the run time was 2.5 min. Detection was performed using the transitions 354.1 → 150.3 m / z for LCZ and 320.1 → 150.3 m / z for IS by positive ion electrospray ionization in multiple reaction monitoring (MRM) mode. Method validation was conducted in accordance with U.S. Food and Drug Administration’s regulatory guidelines for bioanalytical method validation. The calibration curves were linear over the concentration range from 2.80 ng/ml to 2038 ng/ml for conjunctiva, cornea and sclera, 2.09 ng/ml to 1019 ng/ml for AH, 2.09 ng/ml to 509.5 ng/ml for iris, 2.09 ng/ml to 203.8 ng/ml for retinal choroid and VH, 2.04 ng/ml to 101.9 ng/ml for lens, with all the squared correlation coefficients (r 2 ) more than 0.99. The accuracy of the method was within the acceptable limit of 89.34%∼112.78% at the lower limit of quantification and other concentrations, Inter-day and intra-day precision values, expressed in terms of RSD (%), in all tissues were within 15% at all concentrations. The mean recoveries of LCZ in rabbit ocular tissues was 84.85%∼100.52%. No interference was found due to matrix components. Luliconazole was stable during the stability studies, including autosampler stability, benchtop stability, freeze/thaw stability and long-term stability. The method was successfully applied to the ocular pharmacokinetic and tissues distribution studies of LCZ in rabbit after topical administration of LCZ ophthalmic drug delivery system.
研究领域:
药理学
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分析化学
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眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2017
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IF 4.159
Jinyu Li,Guoxin Tan,Bingchao Cheng,Dandan Liu,Weisan Pan
To facilitate the hydrophobic drugs modeled by coumarin-6 (Cou-6) acrossing the cornea to the anterior chamber of the rabbit eye, chitosan (CS) derivatives including chitosan-N-acetyl- l -cysteine (CS-NAC), chitosan oligosaccharides (COS) and carboxymethyl chitosan (CMCS) modified nanostructured lipid carriers (NLCs) were designed and characterized. We found that, with similar size distribution and positive charges, different CS derivatives based on NLCs led to distinctive delivery performance. In vivo precorneal retention study on rabbits revealed that these CS derivatives coating exhibited a stronger resistant effect than Cou-6 eye drops and Cou-6-NLC (P < 0.05), moreover, the AUC (0−∞) , C max and MRT (0−∞) of them followed the sequence of CMCS-Cou-6-NLC < COS-Cou-6-NLC < CS-NAC-Cou-6-NLC. Confocal laser fluorescence microscopy (CLSM) for in vitro corneal penetration study showed that COS-, and CS-NAC-coated NLCs penetrated through the whole corneal epithelium barrier (about 40 μm), while CMCS failed to significantly enhance the intraocular drug penetration as expected, displayed a negligible fluorescence at 30 μm deep. In addition, penetration through the intact cornea was achieved and the penetration levels through the ocular tissues were increased thoroughly for the COS and CS-NAC coating ones compared with CMCS-NLC (P < 0.05), and successfully reduced the conjunctival-to-corneal permeability ratio (ratio (C - S/C) ) thus resulted in a higher bioavailability, which was confirmed by ex vivo fluorescence imaging on ocular tissues. In summary, CS-NAC-NLC and COS-NLC are promising ocular drug delivery systems to achieve prolonged precorneal retention, higher corneal permeability and enhanced ocular bioavailability. And comparatively speaking, CS-NAC-NLC possesses the highest potential for ocular drug delivery.
研究领域:
药剂学
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眼科研究
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 11
·e0141467
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IF 3.234
Xiu-Zeng Bi,Wei-Hua Pan,Xin-Ping Yu,Zong-Ming Song,Zeng-Jin Ren,Min Sun,Cong-Hui Li,Kai-Hui Nan
This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro . Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33–8.67 mmHg, whereas that of group C gradually remained at 7.55–10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.
研究领域:
眼科
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2013
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IF 3.554
Lu Xu,Xu Xu,Hao Chen,Xingyi Li
Polymeric nanoparticles have been developed to improve the bioavailability of drugs applied in ocular drug delivery. However, there are few information on ocular biocompatibility of polymeric nanoparticles applied topically onto the eye. In this paper, the ocular biocompatibility and tolerance of methoxy poly(ethylene glycol)–poly(ɛ-caprolactone) (MPEG–PCL) micelles (∼50 nm) were investigated in rabbit eyes after a single intracameral and intravitreal injections. In vitro cytotoxicity assays showed that MPEG–PCL micelles had no apparent cytotoxicity against human corneal epithelial cells (HCEC), human lens epithelial cells (HLEC), and retinal pigment epithelial cells (RPE cells) at micelle concentrations of 0–2 mg/mL. After a single intracameral injection of 0.2 mL MPEG–PCL micelles (200 mg/mL) into rabbit eyes, MPEG–PCL micelles were slowly removed from aqueous humor in a period of 14 days, while the intraocular pressure (IOP) was maintained at nearly the same level for 15 days. Three days after intracameral injection, dual staining of corneal endothelium showed that the endothelial cells were nearly regular hexagon-shape with well-defined organization, similar to normal endothelial cells. Hematoxylin and eosin staining indicated that there was absence of any obvious changes in microstructure of the corneal tissue and retina after a single intracameral and intravitreal injection of 0.2 mL MPEG–PCL micelles (100 mg/mL, 150 mg/mL, and 200 mg/mL). This study provides valuable information (safety and biocompatibility) for biomedical researchers to develop MPEG–PCL micelles as candidates for ocular drug delivery.
研究领域:
药学
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眼科
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Dandan Liu,Jinyu Li,Bingchao Cheng,Qingyin Wu,Hao Pan
This study is focused on further understanding the characteristics of chitosan-N-acetylcysteine surface-modified nanostructured lipid carriers (CS-NAC-NLCs) in their interaction with ocular mucosa. Coumarin-6 (C6)-labeled NLCs, including uncoated NLCs, chitosan hydrochloride (CH)-, and CS-NAC-coated NLCs, were developed using a melt-emulsification technique and subsequently decorated with different types or portions of chitosan derivatives. Mucoadhesion was evaluated ex vivo using a flow-through process with fluorescence detection. The results demonstrated that the presence of CS-NAC on the C6-NLC surface provided the most obvious enhancement in adhesion due to the formation of both noncovalent (ionic) and covalent (disulfide bridges) interactions with mucus chains. Meanwhile, the concentration of CS-NAC in the formulation positively influenced the viscosity of the nanoparticles and hence prolonged their retention in the ocular tissue. Transcorneal penetration studies revealed that CS-NAC-NLC particles were able to penetrate through the entire corneal epithelium primarily via a transcellular route. The transport depth and velocity strongly relied on the modification material and the particle size. Ex vivo fluorescence imaging and in vivo ocular distribution investigations showed that C6 was broadly distributed in rabbit eye tissues and absorbed by aqueous humor after CS-NAC-NLC instillation. In relation to C6 eye drops, CS-NAC-NLCs achieved considerably higher Cmax (4.01-fold), MRT0-∞ (1.87-fold), and AUC0-∞ (16.29-fold) in the aqueous humor. Moreover, the increase in drug absorption was greater in the cornea than in the conjunctiva. Thereby, it is possible to draw a conclusion that CS-NAC-NLCs presented great potential for drug application to the front portion of the eye.
研究领域:
药剂学
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眼科研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Dengming Zhou,Wenxiang Zhu,Hairong Liu,Feng Zhang,Xiaoyu Zhou,Xinyue Zhang,Yang Zhao,Yuting Huang,Xuanchu Duan
Trabeculectomy is the primary surgical approach used to treat glaucoma, but scarring of the filtering passage (filtering bleb) after surgery often leads to treatment failure. To address this issue, we have developed a drug release system called RSG/Pd@ZIF-8 PHBV film. This system enables the sustained release of an anti-fibrosis drug, aiming to prevent scarring. In vitro , the film has the function of continuous Rosiglitazone (RSG) release, with accelerated release after laser irradiation. The antibacterial experiments revealed that the film exhibited antibacterial rates of 87.0 % against E.coli and 97.1 % against S.aureus, respectively. Moreover, we confirmed its efficacy in a rabbit eye model undergoing trabeculectomy. After implantation of the film, we observed a prolonged postoperative period for reducing intraocular pressure (IOP), increased survival rate of filtering blebs, and improved long-term surgical outcomes in vivo . Additionally, the film exhibited excellent biosafety. In summary, the designed sustained-release film in this study possesses the aforementioned functionalities, allowing for the regulation of anti-scarring drug release without causing harm post-surgery. This personalized and precise anti-scarring strategy represents a significant advancement.
研究领域:
眼科
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药学
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生物材料
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外科研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Yuhui Sheng,Xingchen Sun,Jingtian Han,Wei Hong,Jie Feng,Shuyang Xie,Youjie Li,Fangwei Yan,Keke Li,Baocheng Tian
An N -acetylcysteine functionalized chitosan oligosaccharide-palmitic acid conjugate (NAC-COS-PA) with bioadhesive and permeation promoting properties was synthesized to enhance transocular drug delivery. Flurbiprofen (FB) loaded self-assembled NAC-COS-PA nanomicelles (NAC-COS-PA-FB) were prepared and the drug loading was 7.35 ± 0.32%. Human immortalized corneal epithelial (HCE-T) cell cytotoxicity and hen's egg test-chorioallantoic membrane assays confirmed that the conjugate had good biocompatibility. The transportation efficiency of coumarin-6 (C6) loaded nanomicelles in the HCE-T cell monolayer was approximately 1.97 times higher than that of free C6. Decreased intracellular Ca 2+ concentration and cell membrane potential , increased cell membrane fluidity , and reversible changes in the F-actin cytoskeleton are presumed to be responsible for the enhanced drug permeation. NAC-COS-PA exhibited strong binding capacity with mucin and rabbit eyeball. In vivo pharmacokinetics indicated that the area under the curve (AUC 0 – 6 h ) and the maximum concentration (C max ) of NAC-COS-PA-FB were approximately 1.92 and 2.44 times that of the FB solution, respectively. NAC-COS-PA-FB demonstrated the best in vivo anti-inflammatory efficacy compared to unfunctionalized nanomicelles (COS-PA-FB) and FB solution. Consequently, NAC-COS-PA appears to be a promising bioadhesive carrier for ophthalmic delivery.
研究领域:
药学
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药物递送系统
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眼科学
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生物技术
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药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）