A transfersomes hydrogel patch for cutaneous delivery of propranolol hydrochloride: formulation, in vitro, ex vivo and in vivo studies

Abstract

Objective

In this work, a propranolol hydrochloride (PRH) transfersomes loaded cutaneous hydrogel patch was developed for topical drug delivery in the affected area of infantile haemangioma.

Methods

Sodium cholate was used as the edge activator to prepare the transfersomes. Based on the central composite design, transfersomes hydrogel patch formulation was optimised with 48 h cumulative penetration and time lag as response values. Particle sizes and morphology of the prepared transfersomes were assessed. They were loaded in a cutaneous hydrogel patch, after which their skin permeation abilities were evaluated, and histopathological effects were investigated using guinea pigs. Moreover, in vivo pharmacokinetics studies were performed in rats.

Results

The transfersomes system had a encapsulation efficiency of 81.84 ± 0.53%, particle size of 186.8 ± 3.38 nm, polydispersity index of 0.186 ± 0.002, and a zeta potential of −28.6 ± 2.39 mV. Transmission electron microscopy images revealed sphericity of the particles. The ex vivo drug’s penetration of the optimised transfersomes hydrogel patch was 111.05 ± 11.97 μg/cm² through rat skin within 48 h. Assessment of skin tissue did not reveal any histopathological alterations in epidermal and dermal cells. Pharmacokinetic studies showed that skin C_max (68.22 μg/cm²) and AUC_0–24 (1007.33 μg/cm² × h) for PRH transfersomes hydrogel patch were significantly higher than those of commercially available oral dosage form and hydrogel patch without transfersomes. These findings imply that the transfersomes hydrogel patch can prolong drug accumulation in the affected skin area, and reduce systemic drug distribution via the blood stream.

Conclusions

The hydrogel patch-loaded PRH transfersomes is a potentially useful drug formulation for infantile haemangioma.

Keywords:

• Propranolol hydrochloride
• infantile haemangioma
• transfersomes
• cutaneous delivery
• optimisation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was financially by the Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province [2019E10021] and the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant [No. LHDMZ22H300013].