Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel Approach in the treatment of atopic dermatitis

DPK-060 is a synthetic, 17 amino acid peptide, structurally derived from the human protein kininogen. DPK-060 mainly acts by membrane disruption mechanism, thus demonstrating strong broad-spectrum antimicrobial activity against both gram-positive and gram-negative microbes, including methicillin-resistant S. aureus (MRSA) in-vitro and in-vivo. Apart from its antimicrobial effect, DPK-060 also possesses anti-inflammatory activity. In addition, DPK-060 has demonstrated positive results in phase II clinical trials in atopic dermatitis (AD) patients; but was not statistically conclusive due to the instability of DPK-060 as a drug substance in the formulation. Thus, the present investigation was aimed to assess and compare the efficacy of DPK-060 nanostructured lipid (NLC) based gel with conventional formulations (free DPK-060 gel and lotion) in AD mice animal models. DPK-060 loaded NLCs were formulated by meltemulsification technique and loaded into Carbopol 934 P gel and characterized for various physicochemical parameters such as particle size, zeta-potential, shape and surface morphology, rheological parameters, in-vitro drug release, cytotoxicity, cellular uptake, ex-vivo skin permeation/deposition, in-vitro antimicrobial activity, and proteolytic stability studies.

Highlights

• DPK-060 loaded NLCs were prepared by melt-emulsification technique.

• DPK-060 loaded NLC exhibited improved cellular uptake in-vitro and ex-vivo.

• DPK-060 NLC gel demonstrated controlled release and a better permeation profile.

• DPK-060 NLC gel showed a marked reduction in IL-4, IL-6 & TNF-α levels.

• DPK-060 NLC gel demonstrated improvement in AD lesions.

NLCs exhibited 85% encapsulation with 6.7% loading efficacy, a size, and zeta potential of 128.6 nm and -22.5 mv, respectively. Additionally, DPK-060 NLC gel demonstrated controlled release and a better permeation profile in comparison to free DPK-060 gel and lotion. A substantial reduction in pro-inflammatory cytokines levels and improvement in AD lesions was achieved by DPK-060 NLC gel compared to free DPK-060 gel and lotion-based formulations. The present study confirms that DPK-060 NLC gel-based formulation can be an effective, safe, and novel alternative for the treatment of AD.

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Ankit Javia, Late Ambikanandan Misra, Hetal Thakkar,
Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel Approach in the treatment of atopic dermatitis,
Colloids and Surfaces B: Biointerfaces, 2022, 112658, ISSN 0927-7765,
https://doi.org/10.1016/j.colsurfb.2022.112658.