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Augmented ocular uptake and anti-inflammatory efficacy of decorated Genistein-loaded NLCs incorporated in in situ gel.
- Source :
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International journal of pharmaceutics [Int J Pharm] 2024 Sep 05; Vol. 662, pp. 124508. Date of Electronic Publication: 2024 Jul 23. - Publication Year :
- 2024
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Abstract
- Genistein (Gen); a naturally occurring isoflavone, acts as a tyrosine kinase inhibitor and efficiently downregulates inflammatory cytokines, which are pivotal in eye inflammation. Also, Gen suffers from sparse ocular bioavailability due to poor solubility. In this work, nanostructured lipid carriers (NLCs) were successfully fabricated by using solid (stearic acid and compritol) and liquid (oleic acid) lipids. The optimized Gen-loaded NLCs showed a nanosize range of 140-246 nm, ≥ 98 % entrapment efficiency, and controlled release over 48 h. The ζ-potential of NLCs was increased from -27.3 mV to 25-27.4 mV due to surface modification with chitosan (CS) or eudragit RS100 (ERS 100). All NLCs showed prominent biocompatibility with enhanced cellular uptake on corneal stromal fibroblasts. Moreover, the different NLCs were incorporated into a mucoadhesive in situ gel. The optimized in situ gel (G9), containing 20 % poloxamers and 0.5 % hydroxyethyl cellulose, exhibited excellent gelling ability within 10.5 s, gelling temperature at 33.1 ± 0.6 ℃, spreadability diameter of 4.73 ± 0.12 cm, shear-thinning behavior, and 20 min ex vivo mucoadhesion time with drug release for 120 h. The in vivo results showed distinguished permeation and distribution potential for ocular delivery. In vivo anti-inflammatory effects after 3 days of treatment with CS-Gen-NLCs/G9 and ERS-Gen-NLCs/G9 revealed a downregulation of interleukin-6 levels in the cornea and retina compared to the untreated group. Our research highlights the promising anti-inflammatory potential of ERS-Gen-NLCs/G9 as an efficient, non-irritant Gen nanodelivery system for managing anterior and posterior ocular inflammation.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Rabbits
Acrylic Resins chemistry
Lipids chemistry
Nanostructures administration & dosage
Male
Cornea metabolism
Cornea drug effects
Fibroblasts drug effects
Fibroblasts metabolism
Administration, Ophthalmic
Stearic Acids chemistry
Nanoparticles
Oleic Acid chemistry
Delayed-Action Preparations
Humans
Genistein administration & dosage
Genistein pharmacokinetics
Genistein pharmacology
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents pharmacokinetics
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents chemistry
Chitosan chemistry
Drug Carriers chemistry
Gels
Drug Liberation
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 662
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 39053680
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2024.124508