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Protein nanostructure based drug delivery system for the delivery of therapeutic agents to the anterior segment of the eye

A nanostructure, delivery system technology, applied in the direction of drug delivery, drug combination, powder delivery, etc., can solve problems such as promoting recurrence and aggravating infection

Active Publication Date: 2018-10-23
印度科学工业研究所
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, steroid use is a concern because they can exacerbate infection and possibly promote relapse by suppressing host immunity

Method used

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  • Protein nanostructure based drug delivery system for the delivery of therapeutic agents to the anterior segment of the eye
  • Protein nanostructure based drug delivery system for the delivery of therapeutic agents to the anterior segment of the eye
  • Protein nanostructure based drug delivery system for the delivery of therapeutic agents to the anterior segment of the eye

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0163] Example 1: Dissolution of ketoconazole with methyl-β-cyclodextrin:

[0164]Excess ketoconazole was dissolved in 10 ml of milliQ water using 2.5 mM, 5 mM, 7.5 mM, 10 mM, 15 mM and 20 mM methyl-β-cyclodextrin. The contents of each tube were stirred for 3 days until equilibrated. After equilibration, undissolved ketoconazole was isolated by filtration through a 0.45 μm PVDF syringe filter. Then after diluting the sample, the resulting solution was analyzed for ketoconazole content by a Lambda Model UV-Vis spectrophotometer (Perkin Elmer, USA) at 260 nm.

Embodiment 2

[0165] Example 2: Particle Synthesis and Anti-TLR4 Antibody Conjugation:

[0166] Step 1: Nanoparticles were synthesized using a double desolvation method partially modified from the method described by Coester et al. 2000 (Coester et al. 2000). 2.5 g of type B gelatin (Bloom 225) were dissolved in 50 ml of water (5% w / w) under gentle heating (50°C). In the first desolvation step, 50 ml of acetone was quickly added to the gelatin solution. After precipitation of the deposited gelatin fraction, the supernatant containing soluble low molecular weight gelatin was discarded. The precipitate was redissolved again by adding 50 ml of water under gentle heating (50°C). The redissolved gelatin containing the high molecular weight fraction was snap frozen in liquid nitrogen and lyophilized. The lyophilized gelatin was stored at 4 °C until further use. 0.1 g of lyophilized high molecular weight gelatin was dissolved in 10 ml of water under gentle heating (50° C.) and the pH was adjus...

Embodiment 3

[0169] Example 3: Particle size measurement:

[0170] Gelatin nanoparticles were resuspended in PBS, pH 7.4, and analyzed for size and polydispersity in a Nanoparticle Analyzer system (Horiba Scientific).

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Abstract

The present invention describes a multifunctional system in which a nanostructure (size range of about 10-1000 nm) degrades on exposure to an infection and its associated inflammatory milieu. The degraded nanostructures release the encapsulated drug during the process of degradation, where the kinetics of drug release is determined by the severity of the infection and inflammation. This degradation is triggered by proteases secreted by the pathogen, host polymorphonuclear leucocytes and other host cells. The nanostructures are conjugated to anti-TLR (Toll-like receptor) ligands for targeting the corneal epithelium and blocking the inflammatory pathway.

Description

technical field [0001] The present invention provides nanostructure-based drug delivery systems for therapeutic applications. The present invention proposes a drug delivery system based on nanostructures, wherein the nanostructures are loaded with antimicrobial drugs or anti-inflammatory therapeutic agents, the release of which is regulated by the degradation of the nanostructures. Background technique [0002] Corneal tissue consists primarily of a multilayered epithelium, followed by a densely packed layer of collagen bundles known as the stroma, and an innermost unicellular endothelial layer. The stroma consists of relatively few cells, mainly collagen-secreting keratocytes, and a heterogeneous distribution of immune cells (dendritic cells, Langerhans cells, B-lymphocytes, and T-lymphocytes), mostly in the corneal periphery And relatively few are centrally located. In addition to immune cells in the corneal stroma, conjunctiva-associated lymphoid tissue (CALT) and lacri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/68A61K47/69A61P27/02
CPCA61K31/496A61K47/6849A61K47/6931A61P27/02A61K47/61
Inventor 穆罕默德·阿赫桑·萨阿德莫汉·拉奥·钦塔拉吉里
Owner 印度科学工业研究所
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