Proniosomes as Carriers for Enhanced Bioavailability: A Comprehensive Review of Formulation Strategies and Clinical Evidence Over Two Decades (2004–2024)

Abstract

Poor oral bioavailability of BCS Class II and IV drugs remains a central challenge in pharmaceutical development. Proniosomes dry, free flowing powders that spontaneously form niosomes upon hydration have emerged as a powerful platform to overcome this limitation. This review consolidates two decades (2004–2024) of formulation and preclinical/clinical evidence demonstrating bioavailability enhancement by proniosomal drug delivery systems across multiple routes of administration. A structured literature search was conducted using Pub Med, Scopus, and Web of Science databases. Studies reporting pharmacokinetic parameters, encapsulation efficiency, vesicle characterization, and in vivo bioavailability data were included and synthesized. Proniosomes consistently improved oral bioavailability by 2.1–5.2-fold across drug classes including antidiabetics, cardiovascular agents, anticancer, anti-inflammatory, and antifungal drugs. Transdermal proniosomal gels enhanced skin flux by 3–4-fold. Critical formulation variables including surfactant HLB value, cholesterol ratio, vesicle size, and carrier type profoundly influence bioavailability outcomes. Proniosomes represent a stable, cost-effective, and scalable vesicular technology with compelling evidence of bioavailability enhancement. Regulatory advancement and further clinical trials are needed to fulfill their commercial potential.