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Formulation and Evaluation of Novel Thiolated Intra Pocket Periodontal Composite Membrane of Doxycycline

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Abstract

Localized intra-pocket, retentive, biodegradable, prolonged release thiolated membrane can provide an improved therapeutic efficacy of doxycycline at the site of action with evading off target side effects. To this end, thiolated chitosan-hyaluronic acid composite polymeric complex next-generation of the periodontal membrane was manufactured by solvent casting method. FTIR spectroscopic analysis displayed successful immobilization of thiol groups on the manufactured thiolated periodontal membrane. Moreover, XRD, DSC, AFM and TGA of the membrane confirmed the compatibility of ingredients and modifications in surface chemistry. The thiolated periodontal film was also investigated in terms of thickness, weight uniformity, water-uptake capacity, drug content, pH, entrapment efficiency, lysozymal degradation and release patterns. Also, mucoadhesion profile was explored on gingival mucosa. The immobilized thiol groups on thiolated chitosan and thiolated hyaluronate were found to be 168 ± 11 μM/g (mean ± SD, n = 3) and 189 ± 8 μM/g (mean ± SD, n = 3) respectively. Swelling capacity of the thiolated periodontal membrane was significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. The obtained thiolated membrane depicted 3 -old higher mucoadhesive features as compared to the un-modified membrane. In vitro release kinetics indicated approximately more than 80% prolonged release within 7 days. Mechanical strength of the Thiolated bandage was also significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. Ex-vivo retention study revealed enhanced retention of thiolated membrane as compared to unmodified membrane. In-vitro antimicrobial studies demonstrated that thiolated membrane could efficiently kill Porphyromonas gingivalis cells as compared to the native membrane. Moreover, ex-vivo biodegradation results indicated that 90% of the thiolated membrane was biodegradable in 28 days. Based on these findings, thiolated next-generation of the periodontal membrane seems to be promising for periodontitis therapy.

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Authors and Affiliations

  1. Department of Pharmacy, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Asma Kanwal, Ali Iqbal, Rabia Arshad, Sobia Razzaq & Gul Shahnaz

  2. Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Asma Kanwal, Ali Iqbal, Rabia Arshad, Sobia Razzaq & Gul Shahnaz

  3. Department of Entomology, University College of Agriculture & Environmental Sciences, The Islamia University, Bahawalpur, Pakistan

    Sohail Akhtar

  4. School of Chemical and Material Engineering, NUST, Islamabad, Pakistan

    Nasir Mahmood Ahmad

  5. Comsats University Islamabad, Vehari Campus, Islamabad, Pakistan

    Hina Naz

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  1. Asma Kanwal
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  2. Ali Iqbal
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  8. Gul Shahnaz
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Correspondence to Gul Shahnaz.

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Kanwal, A., Iqbal, A., Arshad, R. et al. Formulation and Evaluation of Novel Thiolated Intra Pocket Periodontal Composite Membrane of Doxycycline. AAPS PharmSciTech 20, 325 (2019). https://doi.org/10.1208/s12249-019-1536-3

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