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Novel Gellan Gum-Based In Situ Nanovesicle Formulation of Docetaxel for Its Localized Delivery Using Depot Formation

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Abstract

In the present study, different in situ hydrogel formulations of docetaxel (DTX) based on biocompatible polymers such as Hyaluronic Acid (HA), poloxamer-407, chitosan and gellan gum were formulated to increase its therapeutic efficacy and reduce toxicity. DTX was loaded in nanovesicles (20 mg/mL equivalent to commercial strength) and further incorporated into the hydrogel bases to possess a dual rationale of protection against burst release and enhanced solubility of the drug. The optimized hydrogel formulation (NV-TPGS-3-GG-4) showed ideal rheological behavior and in situ characteristics at 37±0.5°C with sustained release of more than 144 h. The optimized formulation had instant in vitro gelation (2.8±0.3 min) with good injectability in comparison to the conventional commercial DTX injectable formulation having instant release (<2 h). Additionally, developed formulation exhibited an improved biodisponibility (25.1±0.2 h) in comparison to the commercially available formulation (1.7±0.1 h). The Solid Tumor Carcinoma model in Swiss albino mice revealed that the optimized formulation (based on gellan gum) showed better tumor reduction (85.7±1.2%) and lower toxicity as compared to the commercial formulation (77.3±1.3%). Pharmacokinetic and biodistribution studies demonstrated 3 to 4 times higher localization of drug in tumors. Our findings suggested that injectable gellan gum-based in situ hydrogel formulation can be an effective delivery system for DTX with enhanced solubility, reduced toxicity, and better targeting to the tumors for improved therapeutics.

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Acknowledgements

Authors are thankful to the Department of Science of Technology (DST), New Delhi, India for providing financial support [Sanction no. EMR/2017/003648]. We are grateful to Government Medical College, Amritsar, Punjab, India for providing a facility for histopathology and IIIM, Jammu for cell line analysis and anticancer activity. Authors are also grateful to University Grant Commission (UGC), New Delhi to provide grants in aid to Guru Nanak Dev University, Amritsar under Rashtriya Uchchatar Shiksha Abhiyan (RUSA 2.0) Component 4.0 scheme.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Amrinder Singh, Shubham Thakur & Subheet Kumar Jain

  2. Department of Food Science and Technology, Guru Nanak Dev University, Amritsar, 143005, India

    Narpinder Singh

  3. Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Satwinderjeet Kaur

  4. Department of Open and Distance Learning, Guru Nanak Dev University, Amritsar, 143005, India

    Subheet Kumar Jain

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  1. Amrinder Singh
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Correspondence to Subheet Kumar Jain.

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Singh, A., Thakur, S., Singh, N. et al. Novel Gellan Gum-Based In Situ Nanovesicle Formulation of Docetaxel for Its Localized Delivery Using Depot Formation. AAPS PharmSciTech 22, 165 (2021). https://doi.org/10.1208/s12249-021-02033-7

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