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Cyclodextrin/Adamantane-Grafted Polyethylene Glycol–Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies

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Abstract

Topical formulation of non-steroidal anti-inflammatory drugs (NSAIDs) exhibits many advantages over the oral administration route, such as avoiding the direct effect on GIT and avoiding the poor oral bioavailability of such drugs. Our study aims to develop a new self-assembling construct based on the hydrophobic interaction between adamantane terminated poly (ethylene glycol) polymers and polymerized β-cyclodextrin. The viscous constructs were developed from direct mixing of host and guest polymer solutions, indicating spontaneous formation without cross-linkers. The modified system was evaluated by different analyses, including X-ray diffractometry, electron microscopy, isothermal titration calorimetry, and rheological analysis. Moreover, such a system’s ability for drug loading and release was investigated via the in vitro release of ketorolac tromethamine (KT) as a model of NSAIDs. Finally, the prepared formulas were applied on a rat paw edema model to prove the enhanced anti-inflammatory activities. The obtained results indicated that the modified constructs have a rubbery porous structure with an amorphous nature. Also, from rheological results, the modified system exhibited a viscous behavior with higher loss modulus (G″) compared with storage (G′). The inclusion complexation between cyclodextrin and adamantane moieties was proved by the recorded high binding constants with a 1:1 stoichiometric ratio. Furthermore, the results showed the successful KT incorporation into the modified system and quantitatively released through a semi-permeable membrane in a sustained fashion (over 24 h). Finally, the in vivo results of the medicated constructs showed a significant inhibition of the induced inflammation and swelling, indicating that the modified construct has a great utility for safe non-irritating topical delivery applications.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt

    Ahmed A. H. Abdellatif, Ahmed M. Mohammed, Gamal Zayed, Saleh Abd El-Rasoul & Shaaban K. Osman

  2. Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia

    Ahmed A. H. Abdellatif

  3. Department of Pharmaceutical Sciences, Faculty of Clinical Pharmacy, Albaha University, Allbaha, Saudi Arabia

    Saleh Abd El-Rasoul

  4. Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia

    Saud Almawash

  5. Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, 11961, Egypt

    Mohamed A. Safwat

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  1. Ahmed A. H. Abdellatif
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  4. Saleh Abd El-Rasoul
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Contributions

Conceptualization, Ahmed A. H. Abdellatif and Shaaban K. Osman; data curation, Gamal Zayed; formal analysis, Ahmed M. Mohammed and Shaaban K. Osman; investigation, Ahmed A. H. Abdellatif and Shaaban K. Osman; methodology, Shaaban K. Osman; project administration, Ahmed A. H. Abdellatif, Saleh Abd El-Rasoul, and Shaaban K. Osman; resources, Ahmed A. H. Abdellatif, Gamal Zayed, Saud A. Almawash, and Shaaban K. Osman; software, Ahmed M. Mohammed and Mohamed A. Safwat; validation, Ahmed A. H. Abdellatif and Saleh Abd El-Rasoul; visualization, Saleh Abd El-Rasoul, Saud A. Almawash, Mohamed A. Safwat, and Shaaban K. Osman; writing — original draft, Ahmed M. Mohammed, Gamal Zayed, and Shaaban K. Osman; writing — review and editing, Ahmed A. H. Abdellatif and Shaaban K. Osman.

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Correspondence to Shaaban K. Osman.

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The procedures were approved by the Animal Ethics Committee of Al-Azhar University, Faculty of Pharmacy, Assiut, Egypt (Approval No. AZ-AS/PH/3/C/2021).

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Abdellatif, A.A.H., Mohammed, A.M., Zayed, G. et al. Cyclodextrin/Adamantane-Grafted Polyethylene Glycol–Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies. AAPS PharmSciTech 23, 45 (2022). https://doi.org/10.1208/s12249-021-02188-3

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