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Systematically Optimized Imiquimod-Loaded Novel Hybrid Vesicles by Employing Design of Experiment (DoE) Approach with Improved Biocompatibility, Stability, and Dermatokinetic Profile

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Abstract

The present research work explored the possibility of harnessing the benefits of vesicular carriers for overcoming imiquimod-associated complaints or side effects. Hybrid vesicles were prepared by the most common and easily scalable method, i.e., thin film hydration. The chaffing of myriad of factors, both process and material related, affecting the desirable attributes of conceived vesicles, was performed through Taguchi design. Based upon the analysis of Pareto chart and prior experiences, concentration of phospholipid and poloxamer 407 was selected for optimization by 2 levels, 13 run central composite design (CCD). The optimized hybrid vesicles contained 1% w/v phospholipid and 3% w/v poloxamer 407. The optimized hybrid vesicles were incorporated into the 3% w/v carbopol 940 gel and characterized for morphology, physicochemical properties, and rheological behavior. The release (%) and skin retention (% of total dose) across rat skin from gel at same amount of formulation was more than Imiquad®. The gel delivered the loaded cargo, preferably, in the viable region of skin and formed local depot in confocal microscopic studies. The gel followed one compartment open body dermatokinetic model in rat skin. There was not any harmful effect on the mice skin after repeated applications. The gel was stable at room conditions for 1 year.

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Abbreviations

CCD:

Central composite design

J ss :

Study state permeation flux

USA:

United State of America

FESEM:

Field emission scanning electron microscope

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Acknowledgments

The authors acknowledge Stat-Ease, Inc. Minneapolis, USA, for providing requisite software (Design Expert v10.0) to Mr. Gajanand Sharma, Panjab University, Chandigarh to perform optimization studies with his expert advice. The various department of the Panjab University Chandigarh viz., Department of Geology, Centre for Potential in Excellence in Basic Medical Sciences and UGC Center of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, and SAIF, CIL, and UCIM as well as sections of UIPS have helped in completing the research work and authors acknowledge the contribution of their authorities, staff, and students.

Funding

This work was supported by the University Grant Commission, New Delhi (F.4-1/2006 (BSR)/5-94/2007 (BSR) dated 03.05.2013 and 7858/UIPS date 14/3/14).

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Author notes

  1. Mandeep Sharma and Gajanand Sharma contributed equally to this work.

Authors and Affiliations

  1. University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160014, India

    Mandeep Sharma, Gajanand Sharma, Bhupinder Singh & Om Prakash Katare

  2. UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, 160 014, India

    Bhupinder Singh

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  1. Mandeep Sharma
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Correspondence to Om Prakash Katare.

Ethics declarations

All animal studies were approved by Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) of Panjab University (Approval number- PU/45/99/CPCSEA/IAEC/2018/117).

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The authors declare that they have no conflict of interest.

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Sharma, M., Sharma, G., Singh, B. et al. Systematically Optimized Imiquimod-Loaded Novel Hybrid Vesicles by Employing Design of Experiment (DoE) Approach with Improved Biocompatibility, Stability, and Dermatokinetic Profile. AAPS PharmSciTech 20, 156 (2019). https://doi.org/10.1208/s12249-019-1331-1

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