(T0930-01-03) Formulation and Evaluation of Silymarin Proniosomes for Enhanced Solubility, Bioavailability, and Therapeutic Efficacy

Purpose: The purpose of this study was to develop silymarin-loaded proniosomes to enhance the solubility, bioavailability, and therapeutic efficacy of silymarin, addressing its challenges of poor aqueous solubility and low systemic absorption. By utilizing a proniosomal drug delivery approach, the study aimed to overcome these limitations, providing a stable, scalable, and efficient formulation strategy with the potential to improve therapeutic outcomes and broaden the clinical application of silymarin.

Methods: Proniosome encapsulating silymarin were prepared using the slurry method with Span 60, cholesterol at varying concentrations, and maltodextrin as a carrier. The mixture was dried using a rotary evaporator. Subsequently, the resulting powder was dry and free-flowing. The proniosome powders were characterized for surface morphology and flow properties, entrapment efficiency and in vitro drug release. The harmacokinetic profile of orally administered silymarin loaded proniosome and silymarin drug was investigated.

Results: The proniosomal powder exhibited a lower angle of repose compared to the pure carrier powder maltodextrin (Table 1), indicating improved flow properties. The entrapment efficiency (%EE) of the proniosomal formulations ranged from 56.66 ± 0.65% (F6) to 82.47 ± 1.42% (F3), as shown in Table 1. Surface morphology analysis revealed a smooth surface for the proniosome formulation (Figure 1). Upon hydration, the proniosomal formulations readily formed niosomal vesicles (Figure 1.B). Formulation F4 demonstrated the highest cumulative drug release over 24 hours (86.43% ± 1.23%), indicating that the proniosomes effectively facilitated sustained drug release compared to conventional formulations (Figure 2.A). The in vivo pharmacokinetic profile of silymarin from the proniosomes showed a substantial enhancement in bioavailability (AUC = 41.89 h⋅µg/mL) compared to the free drug (AUC = 3.36 h⋅µg/mL). This finding highlights the potential of proniosomes as a delivery system to improve therapeutic outcomes. Additionally, the time to reach maximum concentration (Tmax) was significantly prolonged for the proniosomal formulation (4 hours) compared to the free drug (2 hours). The maximum concentration (Cmax) of silymarin achieved by the proniosome (5.84 µg/mL) was substantially higher than that of the free drug (0.5 µg/mL), demonstrating the formulation's capacity for improved drug absorption.

Conclusion: The development of silymarin-loaded proniosomes effectively overcame the challenges of poor solubility and low bioavailability associated with silymarin, offering a promising alternative to conventional delivery systems. The optimized formulation demonstrated excellent entrapment efficiency, sustained drug release, and significantly enhanced bioavailability, as evidenced by superior pharmacokinetic parameters compared to the free drug. This study highlights the potential of proniosomes as a versatile and efficient drug delivery system, justifying further research and clinical evaluation for broader therapeutic applications.

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Acknowledgements: The authors declare no conflict of interest.


Figure 1. (A) SEM image of proniosomal powder. (B) TEM image of Niosomal silymarin after hydration of the powdered proniosomes (F4).


Table 1. %EE and Angle of Repose for the developed formulation.


Figure 3. (A) In vitro drug release. (B) In vivo pharmacokinetic profile.