Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study
Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be mini...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Gels |
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| Online Access: | https://www.mdpi.com/2310-2861/8/11/687 |
| _version_ | 1797468257287929856 |
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| author | Omar Awad Alsaidan Ameeduzzafar Zafar Mohd Yasir Sami I. Alzarea Mohammed Alqinyah Mohammad Khalid |
| author_facet | Omar Awad Alsaidan Ameeduzzafar Zafar Mohd Yasir Sami I. Alzarea Mohammed Alqinyah Mohammad Khalid |
| author_sort | Omar Awad Alsaidan |
| collection | DOAJ |
| description | Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box–Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer–Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm<sup>2</sup>) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (<i>p</i> < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP. |
| first_indexed | 2024-03-09T19:03:54Z |
| format | Article |
| id | doaj.art-c9615c6b5ae64a958a2ab0c42c44d5b7 |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-09T19:03:54Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj.art-c9615c6b5ae64a958a2ab0c42c44d5b72023-11-24T04:46:06ZengMDPI AGGels2310-28612022-10-0181168710.3390/gels8110687Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial StudyOmar Awad Alsaidan0Ameeduzzafar Zafar1Mohd Yasir2Sami I. Alzarea3Mohammed Alqinyah4Mohammad Khalid5Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmacy, College of Health Sciences, Arsi University, Asella 396, EthiopiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaConventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box–Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer–Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm<sup>2</sup>) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (<i>p</i> < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP.https://www.mdpi.com/2310-2861/8/11/687ocular deliveryciprofloxacinbilosomesin-situ gelHET-CAMantimicrobial |
| spellingShingle | Omar Awad Alsaidan Ameeduzzafar Zafar Mohd Yasir Sami I. Alzarea Mohammed Alqinyah Mohammad Khalid Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study Gels ocular delivery ciprofloxacin bilosomes in-situ gel HET-CAM antimicrobial |
| title | Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study |
| title_full | Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study |
| title_fullStr | Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study |
| title_full_unstemmed | Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study |
| title_short | Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study |
| title_sort | development of ciprofloxacin loaded bilosomes in situ gel for ocular delivery optimization in vitro characterization ex vivo permeation and antimicrobial study |
| topic | ocular delivery ciprofloxacin bilosomes in-situ gel HET-CAM antimicrobial |
| url | https://www.mdpi.com/2310-2861/8/11/687 |
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