Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate
This study investigates the development of topically applied non-invasive chitosan-nanoparticles (CSNPs) for ocular delivery of tedizolid phosphate (TZP) for the treatment of MRSA-related ocular and orbital infections. An ionic-gelation method was used to prepare TZP-encapsulated CSNPs using tripoly...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/7/2326 |
| _version_ | 1797438355616563200 |
|---|---|
| author | Mohd Abul Kalam Muzaffar Iqbal Abdullah Alshememry Musaed Alkholief Aws Alshamsan |
| author_facet | Mohd Abul Kalam Muzaffar Iqbal Abdullah Alshememry Musaed Alkholief Aws Alshamsan |
| author_sort | Mohd Abul Kalam |
| collection | DOAJ |
| description | This study investigates the development of topically applied non-invasive chitosan-nanoparticles (CSNPs) for ocular delivery of tedizolid phosphate (TZP) for the treatment of MRSA-related ocular and orbital infections. An ionic-gelation method was used to prepare TZP-encapsulated CSNPs using tripolyphosphate-sodium (TPP) as cross-linker. Particle characterization was performed by the DLS technique (Zeta-Sizer), structural morphology was observed by SEM. The drug encapsulation and loading were determined by the indirect method. In-vitro release was conducted through dialysis bags in simulated tear fluid (pH 7) with 0.25% Tween-80. Physicochemical characterizations were performed for ocular suitability of CSNPS. An antimicrobial assay was conducted on different strains of Gram-positive bacteria. Eye-irritation from CSNPs was checked in rabbits. Transcorneal flux and apparent permeability of TZP from CSNPs was estimated through excised rabbit cornea. Ionic interaction between the anionic and cationic functional groups of TPP and CS, respectively, resulted in the formation of CSNPs at varying weight ratios of CS/TPP with magnetic stirring (700 rpm) for 4 h. The CS/TPP weight ratio of 3.11:1 with 10 mg of TZP resulted in optimal-sized CSNPs (129.13 nm) with high encapsulation (82%) and better drug loading (7%). Release profiles indicated 82% of the drug was released from the TZP aqueous suspension (TZP-AqS) within 1 h, while it took 12 h from F2 to release 78% of the drug. Sustained release of TZP from F2 was confirmed by applying different release kinetics models. Linearity in the profile (suggested by Higuchi’s model) indicated the sustained release property CSNPs. F2 has shown significantly increased (<i>p</i> < 0.05) antibacterial activity against some Gram-positive strains including one MRSA strain (SA-6538). F2 exhibited a 2.4-fold increased transcorneal flux and apparent permeation of TZP as compared to TZP-AqS, indicating the better corneal retention. No sign or symptoms of discomfort in the rabbits’ eyes were noted during the irritation test with F2 and blank CSNPs, indicating the non-irritant property of the TZP-CSNPs. Thus, the TZP-loaded CSNPs have strong potential for topical use in the treatment of ocular MRSA infections and related inflammatory conditions. |
| first_indexed | 2024-03-09T11:36:36Z |
| format | Article |
| id | doaj.art-ff13bea8e93b4d12a52c2a919c6c29fa |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:36:36Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ff13bea8e93b4d12a52c2a919c6c29fa2023-11-30T23:42:43ZengMDPI AGMolecules1420-30492022-04-01277232610.3390/molecules27072326Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid PhosphateMohd Abul Kalam0Muzaffar Iqbal1Abdullah Alshememry2Musaed Alkholief3Aws Alshamsan4Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaNanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaNanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaNanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaThis study investigates the development of topically applied non-invasive chitosan-nanoparticles (CSNPs) for ocular delivery of tedizolid phosphate (TZP) for the treatment of MRSA-related ocular and orbital infections. An ionic-gelation method was used to prepare TZP-encapsulated CSNPs using tripolyphosphate-sodium (TPP) as cross-linker. Particle characterization was performed by the DLS technique (Zeta-Sizer), structural morphology was observed by SEM. The drug encapsulation and loading were determined by the indirect method. In-vitro release was conducted through dialysis bags in simulated tear fluid (pH 7) with 0.25% Tween-80. Physicochemical characterizations were performed for ocular suitability of CSNPS. An antimicrobial assay was conducted on different strains of Gram-positive bacteria. Eye-irritation from CSNPs was checked in rabbits. Transcorneal flux and apparent permeability of TZP from CSNPs was estimated through excised rabbit cornea. Ionic interaction between the anionic and cationic functional groups of TPP and CS, respectively, resulted in the formation of CSNPs at varying weight ratios of CS/TPP with magnetic stirring (700 rpm) for 4 h. The CS/TPP weight ratio of 3.11:1 with 10 mg of TZP resulted in optimal-sized CSNPs (129.13 nm) with high encapsulation (82%) and better drug loading (7%). Release profiles indicated 82% of the drug was released from the TZP aqueous suspension (TZP-AqS) within 1 h, while it took 12 h from F2 to release 78% of the drug. Sustained release of TZP from F2 was confirmed by applying different release kinetics models. Linearity in the profile (suggested by Higuchi’s model) indicated the sustained release property CSNPs. F2 has shown significantly increased (<i>p</i> < 0.05) antibacterial activity against some Gram-positive strains including one MRSA strain (SA-6538). F2 exhibited a 2.4-fold increased transcorneal flux and apparent permeation of TZP as compared to TZP-AqS, indicating the better corneal retention. No sign or symptoms of discomfort in the rabbits’ eyes were noted during the irritation test with F2 and blank CSNPs, indicating the non-irritant property of the TZP-CSNPs. Thus, the TZP-loaded CSNPs have strong potential for topical use in the treatment of ocular MRSA infections and related inflammatory conditions.https://www.mdpi.com/1420-3049/27/7/2326tedizolid-phosphatechitosannanoparticlesantibacterialeye-irritation transcorneal-permeation |
| spellingShingle | Mohd Abul Kalam Muzaffar Iqbal Abdullah Alshememry Musaed Alkholief Aws Alshamsan Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate Molecules tedizolid-phosphate chitosan nanoparticles antibacterial eye-irritation transcorneal-permeation |
| title | Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate |
| title_full | Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate |
| title_fullStr | Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate |
| title_full_unstemmed | Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate |
| title_short | Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate |
| title_sort | development and evaluation of chitosan nanoparticles for ocular delivery of tedizolid phosphate |
| topic | tedizolid-phosphate chitosan nanoparticles antibacterial eye-irritation transcorneal-permeation |
| url | https://www.mdpi.com/1420-3049/27/7/2326 |
| work_keys_str_mv | AT mohdabulkalam developmentandevaluationofchitosannanoparticlesforoculardeliveryoftedizolidphosphate AT muzaffariqbal developmentandevaluationofchitosannanoparticlesforoculardeliveryoftedizolidphosphate AT abdullahalshememry developmentandevaluationofchitosannanoparticlesforoculardeliveryoftedizolidphosphate AT musaedalkholief developmentandevaluationofchitosannanoparticlesforoculardeliveryoftedizolidphosphate AT awsalshamsan developmentandevaluationofchitosannanoparticlesforoculardeliveryoftedizolidphosphate |