Development and Optimization of Transferosomal Gel for Efficient Topical Delivery of Berberine Hydrochloride
Authors: Deshkar Sanjeevani S. , Halyali Arati S. , Thomas Asha B. , Undale Vaishali R. , Pagar Roshani R. , Nagore Dheeraj N. 
Published: November 2024

Background:

Berberine is an isoquinoline alkaloid with potent anti-inflammatory effects.
However, its therapeutic efficacy is often restricted by its poor solubility, absorption, and
permeability, especially in topical applications. Transferosomes are elastic vesicular carriers with
high skin permeability values and retention, making them suitable for encapsulating hydrophilic
and lipophilic actives.

Objective:

The objective of this research was to develop a transferosome-based topical gel formulation
of Berberine hydrochloride (BER) to improve its skin permeability and anti-inflammatory
efficacy.

Method:

The thin film hydration method was used to formulate the BER transferosomes. The effects
of independent variables, amount of BER in lipid phase (X1), and lipid (Phospholipon 90G)
to surfactant ratio (X2) on BER entrapment and vesicle size were studied using face-centered central
composite design. The characterization was performed using differential scanning calorimetry,
transmission electron microscopy, and X-ray diffraction. The optimized batch (F5) was incorporated
in Carbopol gel and further investigated for viscosity, in vitro and ex-vivo diffusion, skin
retention by tape stripping, and in-vivo anti-inflammatory efficiency.

Results:

The formulation optimized with 50 mg of drug and a 5:1 lipid-to-surfactant ratio (F5) demonstrated
higher drug entrapment efficiency (72.11%) and lower vesicle size (77.9 nm). TEM
validated the spherical vesicle morphology, whereas DSC and XRD analysis confirmed the molecular
entrapment of BER within the phospholipid vesicles. The transferosomal gel demonstrated improved
BER diffusion (0.63 mg/cm2) confirmed by in vitro and ex-vivo diffusion experiments that
revealed a 6-fold increase in flux and permeability coefficient (0.1053 mg. cm-2.h-1). The drug release
from transferosome gel was non-Fickian in nature (n = 0.6575), indicating an integration of
diffusion and erosion processes. Furthermore, BER transferosomal gel displayed substantial anti-
inflammatory activity in rats (p < 0.001).

result:

The independent variables exerted a substantial impact on drug entrapment and transferosome vesicle size. The optimized batch (F5) exhibited 72.11 % of BER entrapment and 77.9 nm vesicle size. DSC studies indicated molecular dispersion of BER in phospholipon G. The change in BER crystalline state was indicated by the XRD study. In vitro, diffusion study of Transferosome gel formulation indicated the sustained release by a non-fickian mechanism. Ex vivo skin permeation revealed significant improvement in BER permeation (p< 0.05). Further, the tape-stripping method revealed higher BER skin permeability. In-vivo anti-inflammatory efficacy of BER transferosome gel was significantly higher as compared to plain BER gel.

Conclusion:

The findings demonstrated the potential of transferosomal gel as a promising approach
for efficient drug delivery and therapeutic efficacy.