Development and Evaluation of Chitosan Nanoparticles for Ocular Delivery of Tedizolid Phosphate

被引:23
作者
Abul Kalam, Mohd [1 ,2 ]
Iqbal, Muzaffar [3 ,4 ]
Alshememry, Abdullah [1 ,2 ]
Alkholief, Musaed [1 ,2 ]
Alshamsan, Aws [1 ,2 ]
机构
[1] King Saud Univ, Coll Pharm, Dept Pharmaceut, Nanobiotechnol Unit, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Coll Pharm, Dept Pharmaceut, Riyadh 11451, Saudi Arabia
[3] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh 11451, Saudi Arabia
[4] King Saud Univ, Coll Pharm, Bioavailabil Unit, Cent Lab, Riyadh 11451, Saudi Arabia
来源
MOLECULES | 2022年 / 27卷 / 07期
关键词
tedizolid-phosphate; chitosan; nanoparticles; antibacterial; eye-irritation transcorneal-permeation; RESISTANT STAPHYLOCOCCUS-AUREUS; SOLID LIPID NANOPARTICLES; IN-VITRO RELEASE; DRUG-DELIVERY; HYALURONIC-ACID; MICROSPHERES; OXAZOLIDINONE; FORMULATION; SURFACE; SKIN;
D O I
10.3390/molecules27072326
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (p < 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.
引用
收藏
页数:22
相关论文
共 69 条
  • [41] Stability of Crushed Tedizolid Phosphate Tablets for Nasogastric Tube Administration
    Kennedy G.
    Osborn J.
    Flanagan S.
    Alsayed N.
    Bertolami S.
    [J]. Drugs in R&D, 2015, 15 (4) : 329 - 333
  • [42] Chitosan coated PLGA nanoparticles amplify the ocular hypotensive effect of forskolin: Statistical design, characterization and in vivo studies
    Khan, Nazia
    Ameeduzzafar
    Khanna, Kushagra
    Bhatnagar, Aseem
    Ahmad, Farhan Jalees
    Ali, Asgar
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2018, 116 : 648 - 663
  • [43] Tedizolid: A new oxazolidinone antimicrobial
    Kisgen, Jamie
    Mansour, Hanine
    Unger, Nathan
    Childs, Lindsey
    [J]. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 2014, 71 (08) : 621 - 633
  • [44] Prospection of recent chitosan biomedical trends: Evidence from patent analysis (2009-2020)
    Kurakula, Mallesh
    Raghavendra, Naveen N.
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2020, 165 (165) : 1924 - 1938
  • [45] In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma
    Kurakula, Mallesh
    Naveen, N. Raghavendra
    [J]. MARINE DRUGS, 2020, 18 (04)
  • [46] Solid lipid nanoparticles for transdermal delivery of avanafil: optimization, formulation, in-vitro and ex-vivo studies
    Kurakula, Mallesh
    Ahmed, Osama A. A.
    Fahmy, Usama A.
    Ahmed, Tarek A.
    [J]. JOURNAL OF LIPOSOME RESEARCH, 2016, 26 (04) : 288 - 296
  • [47] Alternatives to in vivo Draize rabbit eye and skin irritation tests with a focus on 3D reconstructed human cornea-like epithelium and epidermis models
    Lee M.
    Hwang J.-H.
    Lim K.-M.
    [J]. Toxicological Research, 2017, 33 (3) : 191 - 203
  • [48] Moore J., 1984, J Am Coll Toxicol, V3, P1
  • [49] Miscibility study of chitosan/2-hydroxyethyl starch blends and evaluation of their effectiveness as drug sustained release hydrogels
    Nanaki, Stavroula G.
    Koutsidis, Ioannis A.
    Koutri, Ioanna
    Karavas, Evangelos
    Bikiaris, Dimitrios
    [J]. CARBOHYDRATE POLYMERS, 2012, 87 (02) : 1286 - 1294
  • [50] Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome
    Narita, Masashi
    Tsuji, Brian T.
    Yu, Victor L.
    [J]. PHARMACOTHERAPY, 2007, 27 (08): : 1189 - 1197