Withdrawal Notice: Developing a Nanoemulsion for Permeation of Peptides of Bee Venom through the Skin

Abstract

Background: Nanoemulsions (NEs) are capable of facilitating drug permeation through the skin. Bee venom (BV) contains peptides that do not pass through healthy skin due to their high molecular weight. Methods: We prepared water-in-oil (W/O) NEs containing BV with a mixture of Span 80, Tween 80, and olive oil by low energy method. Then, based on stability studies, four different NE formulations with 3, 5, 7, and 9% aqueous phase were chosen, each having different BV concentrations and characterized for their particle size polydispersity index (PDI), viscosity, and refractive index. Afterward, an NE preparation having 5% BV solution was used for skin permeation studies by Franz diffusion cell at three BV concentrations (i.e., 5000, 2500, and 1250 µg/ml). Result: The results showed that by increasing the percentage of BV content (from 3 to 9 %) and surfactants (from 30 to 60 %), the size of NEs decreased while increasing BV concentration at a fixed percentage of BV content, led to increase in size and PDI. Skin permeation studies showed that after 12 h, NEs could permeate approximately 10 % of initial BV through the skin, depending on BV concentration in the NE. Conclusion: In conclusion, the data showed that NEs could be used for topical delivery of peptides of BV through the skin.

Current challenges ahead in preparation, characterization, and pharmaceutical applications of nanoemulsions

“…The low‐energy method is straightforward, but requires high content of surfactant/co‐surfactant (Meinzer, 1995). The high concentration of surfactant/co‐surfactant not only increases the toxicity, but also may directly (Bouchemal et al, 2004) or inversely (Yousefpoor, Amani, Divsalar, & Vafadar, 2022) alter the size. Low energy methods are favorite methods for many researchers as they are mild processes for sensitive molecules and do not require expensive equipment (Yukuyama et al, 2016).…”

“…Usually, aqueous phase of NEs is distilled water as it is both safe and inexpensive. Water can also be gelified easily using compounds such as carboxymethyl cellulose (Das et al, 2022;Yousefpoor, Amani, Divsalar, & Vafadar, 2022).…”

“…Usually, aqueous phase of NEs is distilled water as it is both safe and inexpensive. Water can also be gelified easily using compounds such as carboxymethyl cellulose (Das et al, 2022; Yousefpoor, Amani, Divsalar, & Vafadar, 2022). Nevertheless, depending on the solubility of the active ingredient, other solvents may also be added to the aqueous phase.…”

“…It is well‐known that when high oil content is used in the preparation, high surfactant concentration should be used too. This may lead to formation of MEs and coarse emulsions (Bouchemal et al, 2004; Yousefpoor, Amani, Divsalar, & Vafadar, 2022). Another challenge in preparing a stable NE is the ability of the surfactant(s) to “dissolve” certain types of oil molecules.…”

“…Furthermore, the external phase of the NE is usually the phase with greater volume (Singh et al, 2017). When designing an NE, the material to be transported by the NE regulates the NE type: if the material nature is hydrophilic (e.g., plasmid DNA; Wu et al, 2001), ascorbic acid (Zaid Alkilani et al, 2021) or peptide (Yousefpoor, Amani, Divsalar, Mousavi, et al, 2022; Yousefpoor, Amani, Divsalar, & Vafadar, 2022), the NE formulation should be W/O, while if the component nature is hydrophobic (e.g., clotrimazole; Borhade et al, 2012), insulin (M. Simon et al, 2004) and antisense oligonucleotide (Hagigit et al, 2010), the NE should be O/W (Bhatt & Madhav, 2011).…”