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pH Switchable LLC Nanoparticles Targeting Colon: Optimization Using D-Optimal Design

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Abstract

Purpose

To design pH switchable LLC (lyotropic liquid crystal) nanoparticles with the goal of exclusively delivering 5-Fluorouracil (5-FU) in the colonic region of GIT for the treatment of colon cancer.

Methods

The proportions of monoolein (MO), oleic acid (OA), and pluronic F127 were chosen using the quadratic model of D-optimal mixture design for LLC nanoparticle batches. The formulations were characterized and evaluated for (i) adhesion work at porcine stomach, (ii) adhesion work at porcine large intestine, (iii) drug release up to pH 6.8, and (iv) drug release at pH 7.4. The models developed during data analysis were optimized and subjected to pharmacokinetic and in vivo scintigraphic study.

Results

The design proposed three optimal formulations OLN1, OLN2, and OLN3, where OLN3 outperformed the rest in terms of 5-FU release profile as well as comparable work of adhesion at porcine stomach and large intestine. The gamma scintigraphic images and pharmacokinetic results of OLN3 with 30% MO, 62.565% OA, and 7.435% pluronic F127 indicated that the hexagonal configuration of the system prevented 5-FU absorption from the upper GIT and no substantial release of the drug occurred within 6-h period. However, there was considerable release from the system due to hexagonal structure converting to cubic structure at colonic pH.

Conclusions

Upon oral administration, OLN3 preserved its integrity during its passage through stomach, successfully entered, and was evenly spread in the colon during the 12-h study period demonstrating the required properties in terms of drug targeting.

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Acknowledgements

Authors like to thankfully acknowledge Mrs. Pratibha Omray, Technical director, Khandelwal Laboratories Pvt. Ltd. for providing 5-Fluorouracil as gift sample.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, 786004, Assam, India

    Prakash Rajak, Lila Kanta Nath & Biman Bhuyan

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  1. Prakash Rajak
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  2. Lila Kanta Nath
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  3. Biman Bhuyan
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Correspondence to Prakash Rajak.

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Ethics Approval

All procedures of the studies involving animals were in agreement with the recommendation of IAEC of Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam consistent with the guidelines of “Committee for the Purpose of Control and Supervision of Experiments on Animals” (CPCSEA, registration no: 1576/GO/Ere/S/11/ CPCSEA) with approval no. IAEC/DU/101 dated: 06/08/2015.

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The authors declare no competing interests.

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Rajak, P., Nath, L.K. & Bhuyan, B. pH Switchable LLC Nanoparticles Targeting Colon: Optimization Using D-Optimal Design. J Pharm Innov 18, 128–143 (2023). https://doi.org/10.1007/s12247-022-09628-y

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