Skip to content
BY 4.0 license Open Access Published by De Gruyter Open Access December 17, 2021

Development of mucoadhesive thiomeric chitosan nanoparticles for the targeted ocular delivery of vancomycin against Staphylococcus aureus resistant strains

Faryal Jahan, Shahiq uz Zaman, Sohail Akhtar, Rabia Arshad, Ibrahim Muhammad Ibrahim, Gul Shahnaz, Abbas Rahdar and Sadanand Pandey
From the journal Nanofabrication

Abstract

This study aims to formulate mucoadhesive vancomycin loaded thiolated chitosan (TCS) nanoparticles. These nanoparticles are mucoadhesive and enhance the retention of the drug at the ocular site. For this purpose, TCS loaded vancomycin nanoparticles were prepared by the ion-gelation method and were characterized for their size, shape, polydispersity index, mucoadhesion, cellular uptake and anti-inflammatory activity. The average size of the synthesized nanoparticles was found to be 288 nm with positive zeta potential. Moreover, 85% vancomycin was successfully encapsulated in TCS nanoparticles by using this method. A 2-fold increase in mucoadhesion was found as compared to non-thiolated vancomycin formulation (p < 0.05). Zone of inhibition of vancomycin loaded TCS was also significantly improved compared to non-thiolated chitosan nanoparticles and vancomycin alone. In-vivo anti-inflammatory evaluation via histopathology resulted in ocular healing. Based on the results, it is inferred that TCS nanoparticles are a promising drug delivery carrier system for ocular delivery of vancomycin.

References

[1] Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006 Nov;58(11):1131–5.10.1016/j.addr.2006.07.027Search in Google Scholar PubMed

[2] Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010 Sep;12(3):348–60.10.1208/s12248-010-9183-3Search in Google Scholar PubMed PubMed Central

[3] Arshad R, Sohail MF, Sarwar HS, Saeed H, Ali I, Akhtar S, et al. ZnO-NPs embedded biodegradable thiolated bandage for postoperative surgical site infection: in vitro and in vivo evaluation. PLoS One. 2019 Jun;14(6):e0217079.10.1371/journal.pone.0217079Search in Google Scholar PubMed PubMed Central

[4] Gunda S, Hariharan S, Mandava N, Mitra AK. Barriers in ocular drug delivery. Ocular Transporters in Ophthalmic Diseases and Drug Delivery. Springer; 2008. pp. 399–413.10.1007/978-1-59745-375-2_21Search in Google Scholar

[5] Huang D, Chen YS, Rupenthal ID. Overcoming ocular drug delivery barriers through the use of physical forces. Adv Drug Deliv Rev. 2018 Feb;126:96–112.10.1016/j.addr.2017.09.008Search in Google Scholar PubMed

[6] Barar J, Javadzadeh AR, Omidi Y. Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv. 2008 May;5(5):567–81.10.1517/17425247.5.5.567Search in Google Scholar PubMed

[7] Tiwari R, Sethiya NK, Gulbake AS, Mehra NK, Murty US, Gulbake A. A review on albumin as a biomaterial for ocular drug delivery. Int J Biol Macromol. 2021 Nov;191:591–9.10.1016/j.ijbiomac.2021.09.112Search in Google Scholar PubMed

[8] Omerović N, Škrbo S, Vranić E, editors. Tolerance Assays Performed in Animal Models During the Evaluation of Nanoparticles for Ocular Drug Delivery. International Conference on Medical and Biological Engineering; 2021: Springer. https://doi.org/10.1007/978-3-030-73909-6_80.10.1007/978-3-030-73909-6_80Search in Google Scholar

[9] Arshad R, Pal K, Sabir F, Rahdar A, Bilal M, Shahnaz G, et al. A review of the nanomaterials use for the diagnosis and therapy of salmonella typhi. J Mol Struct. 2021;1230:129928.10.1016/j.molstruc.2021.129928Search in Google Scholar

[10] Javed I, Hussain SZ, Ullah I, Khan I, Ateeq M, Shahnaz G, et al. Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B. J Mater Chem B Mater Biol Med. 2015 Nov;3(42):8359–65.10.1039/C5TB01258ASearch in Google Scholar

[11] Wadhwa S, Paliwal R, Paliwal SR, Vyas SP. Nanocarriers in ocular drug delivery: an update review. Curr Pharm Des. 2009;15(23):2724–50.10.2174/138161209788923886Search in Google Scholar PubMed

[12] Kumar A, Malviya R, Sharma PK. Recent trends in ocular drug delivery: a short review. Eur J Appl Sci. 2011;3(3):86–92.Search in Google Scholar

[13] Battaglia L, Serpe L, Foglietta F, Muntoni E, Gallarate M, Del Pozo Rodriguez A, et al. Application of lipid nanoparticles to ocular drug delivery. Expert Opin Drug Deliv. 2016 Dec;13(12):1743–57.10.1080/17425247.2016.1201059Search in Google Scholar PubMed

[14] Rahdar A, Taboada P, Hajinezhad MR, Barani M, Beyzaei H. Effect of tocopherol on the properties of Pluronic F127 microemulsions: physico-chemical characterization and in vivo toxicity. J Mol Liq. 2019;277:624–30.10.1016/j.molliq.2018.12.074Search in Google Scholar

[15] Salimi A, Sharif Makhmal Zadeh B, Godazgari S, Rahdar A. Development and Evaluation of Azelaic Acid-Loaded Microemulsion for Transfollicular Drug Delivery Through Guinea Pig Skin: A Mechanistic Study. Adv Pharm Bull. 2020 Jun;10(2):239–46.10.34172/apb.2020.028Search in Google Scholar PubMed PubMed Central

[16] Mittal N, Kaur G. Investigations on polymeric nanoparticles for ocular delivery. Advances in Polymer Technology. 2019;2019. https://doi.org/10.1155/2019/1316249.10.1155/2019/1316249Search in Google Scholar

[17] Rahdar A, Hajinezhad MR, Nasri S, Beyzaei H, Barani M, Trant JF. The synthesis of methotrexate-loaded F127 microemulsions and their in vivo toxicity in a rat model. J Mol Liq. 2020;313:113449.10.1016/j.molliq.2020.113449Search in Google Scholar

[18] Chen G, Qiu H, Prasad PN, Chen XJCr. Upconversion nanoparticles: design, nanochemistry, and applications in theranostics. 2014;114(10):5161-214.10.1021/cr400425hSearch in Google Scholar PubMed PubMed Central

[19] Rahdar A, Sargazi S, Barani M, Shahraki S, Sabir F, Aboudzadeh MA. Lignin-stabilized doxorubicin microemulsions: Synthesis, physical characterization, and in vitro assessments. Polymers (Basel). 2021 Feb;13(4):641.10.3390/polym13040641Search in Google Scholar PubMed PubMed Central

[20] Zhu X, Su M, Tang S, Wang L, Liang X, Meng F, et al. Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery. Mol Vis. 2012;18:1973–82.Search in Google Scholar

[21] McGuinness WA, Malachowa N, DeLeo FR. Focus: infectious diseases: vancomycin resistance in Staphylococcus aureus. Yale J Biol Med. 2017 Jun;90(2):269–81.Search in Google Scholar

[22] Barani M, Mukhtar M, Rahdar A, Sargazi G, Thysiadou A, Kyzas GZ. Progress in the Application of Nanoparticles and Graphene as Drug Carriers and on the Diagnosis of Brain Infections. Molecules. 2021 Jan;26(1):186.10.3390/molecules26010186Search in Google Scholar PubMed PubMed Central

[23] Hasanein P, Rahdar A, Barani M, Baino F, Yari S. Oil-in-water microemulsion encapsulation of antagonist drugs prevents renal ischemia-reperfusion injury in rats. Appl Sci (Basel). 2021;11(3):1264.10.3390/app11031264Search in Google Scholar

[24] Dippong T, Cadar O, Levei EA, Deac IG. Microstructure, porosity and magnetic properties of Zn0. 5Co0. 5Fe2O4/SiO2 nanocomposites prepared by sol-gel method using different polyols. J Magn Magn Mater. 2020;498:166168.10.1016/j.jmmm.2019.166168Search in Google Scholar

[25] Shahnaz G, Edagwa BJ, McMillan J, Akhtar S, Raza A, Qureshi NA, et al. Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis. Nanomedicine (Lond). 2017 Jan;12(2):99–115.10.2217/nnm-2016-0325Search in Google Scholar PubMed PubMed Central

[26] Buzia OD, Dima C, Dima S. Preparation and characterization of chitosan microspheres for vancomycin delivery. Farmacia. 2015;63(6):897–902.Search in Google Scholar

[27] Batool A, Arshad R, Razzaq S, Nousheen K, Kiani MH, Shahnaz G. Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer. Int J Biol Macromol. 2020 Jun;152:503–15.10.1016/j.ijbiomac.2020.02.275Search in Google Scholar PubMed

[28] Ahmad Z, Khan MI, Siddique MI, Sarwar HS, Shahnaz G, Hussain SZ, et al. Fabrication and characterization of thiolated chitosan microneedle patch for transdermal delivery of tacrolimus. AAPS PharmSciTech. 2020 Jan;21(2):68.10.1208/s12249-019-1611-9Search in Google Scholar PubMed

[29] Baloglu E, Karavana SY, Senyigit ZA, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Technol. 2011 Nov-Dec;16(6):627–36.10.3109/10837450.2010.508074Search in Google Scholar PubMed

[30] Kumar V, Sharma N, Sourirajan A, Khosla PK, Dev K. Comparative evaluation of antimicrobial and antioxidant potential of ethanolic extract and its fractions of bark and leaves of Terminalia arjuna from north-western Himalayas, India. J Tradit Complement Med. 2017 Apr;8(1):100–6.10.1016/j.jtcme.2017.04.002Search in Google Scholar PubMed PubMed Central

[31] Khiev D, Mohamed ZA, Vichare R, Paulson R, Bhatia S, Mohapatra S, et al. Emerging Nano-Formulations and Nanomedicines Applications for Ocular Drug Delivery. Nanomaterials (Basel). 2021 Jan;11(1):173.10.3390/nano11010173Search in Google Scholar PubMed PubMed Central

[32] Zhang P, Zhang N, Wang Q, Wang P, Yuan J, Shen J, et al. Disulfide bond reconstruction: A novel approach for grafting of thiolated chitosan onto wool. Carbohydr Polym. 2019 Jan;203:369–77.10.1016/j.carbpol.2018.09.074Search in Google Scholar PubMed

[33] Arshad R, Tabish TA, Naseem AA, Hassan MR, Hussain I, Hussain SS, et al. Development of poly-L-lysine multi-functionalized muco-penetrating self- emulsifying drug delivery system (SEDDS) for improved solubilization and targeted delivery of ciprofloxacin against intracellular Salmonella typhi. J Mol Liq. 2021;333:115972.10.1016/j.molliq.2021.115972Search in Google Scholar

Received: 2021-10-12
Accepted: 2021-11-24
Published Online: 2021-12-17

© 2020 Faryal Jahan et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Scroll Up Arrow