Polymeric micelles for oral drug delivery: progress and innovations in preclinical studies

Oral drug delivery is a preferred route due to its non-invasive nature and ease of administration, but it faces significant challenges, particularly for poorly water-soluble drugs. These challenges include low aqueous solubility, limited permeability across intestinal membranes, susceptibility to enzymatic degradation, and instability in the gastrointestinal (GI) environment. Such limitations can result in poor bioavailability and inconsistent therapeutic outcomes, highlighting the need for advanced drug delivery strategies. Polymeric micelles, formed by the self-assembly of amphiphilic block copolymers into core-shell nanostructures, offer a promising solution. These micelles enhance the solubility, stability, and permeability of hydrophobic drugs, improving their bioavailability. Preclinical studies have demonstrated the potential of polymeric micelles to protect drugs from enzymatic degradation and harsh gastrointestinal conditions, facilitating their controlled release and absorption across intestinal barriers. Moreover, micelles can be engineered with pH-sensitive or transporter-targeting functionalities, allowing for site-specific drug release within different regions of the GI tract. These properties collectively contribute to enhanced therapeutic efficacy and reduced systemic toxicity. Despite encouraging laboratory findings, the clinical translation of polymeric micelles remains limited, primarily due to challenges related to large-scale manufacturing, long-term stability, and regulatory compliance. Addressing these issues is essential to realize the full potential of polymeric micelle-based oral formulations. Future research should prioritize the development of clinically viable micellar systems through interdisciplinary approaches that integrate polymer science, pharmacokinetics, and regulatory frameworks.