Recent Advances in Bilosomes for the Treatment of Skin Diseases: A Review

Skin diseases affect approximately one third of the world's population and significantly impair quality of life. Common disorders including psoriasis, eczema, acne vulgaris, fungal infections, and skin cancer require prolonged treatment with topical formulations. However, conventional creams, gels, and ointments often exhibit poor skin penetration, limited drug retention, and frequent dosing requirements due to the barrier function of the stratum corneum [1, 2]. Nanotechnology based drug delivery systems have attracted considerable attention for improving topical therapy. Among these, bilosomes are flexible lipid vesicles composed of phospholipids, cholesterol, and bile salts that enhance drug penetration through the skin while protecting encapsulated drugs from degradation [3-4].

Bilosomes

Bilosomes are nanosized lipid vesicles containing phospholipids stabilized with bile salts such as sodium deoxycholate, sodium cholate, or sodium taurocholate. Originally developed for oral vaccine delivery, bilosomes have recently gained importance in topical and transdermal drug delivery because of their enhanced deformability and stability [5].

Figure 1 Structure of Bilosomes

Figure 2 Methods of Preparation of Bilosomes

Patent Landscape

The intellectual property landscape of bilosomes has evolved from oral vaccine delivery toward topical and transdermal therapeutics. Early patents primarily protected bile salt-containing lipid vesicles designed to improve vesicle stability. More recent inventions focus on surface engineering (PEGylation), edge activation, hydrogel incorporation, and hybrid nanovesicular systems that enhance skin penetration and prolong drug retention. These technologies are particularly attractive for chronic dermatological disorders because they reduce dosing frequency while minimizing systemic drug exposure.  Recent innovations have introduced PEGylated bilosomes, which exhibit prolonged residence time within the skin and improved physicochemical stability. Similarly, edge-activated bilosomes (limobilosomes) incorporating terpenes such as limonene have demonstrated markedly improved intradermal deposition and therapeutic efficacy against melanoma in preclinical investigations, representing a promising direction for future patent development.  Commercial translation of bilosomes remains in its early stages. The relatively small number of granted patents suggests that substantial opportunities remain for protecting innovations involving drug combinations, stimuli-responsive bilosomes, targeted dermatological therapies, microneedle assisted bilosomal delivery, and hydrogel based sustained release systems.

FUTURE PERSPECTIVES

Future research on bilosomal drug delivery systems for skin diseases should prioritize well designed clinical trials to establish their long term safety, therapeutic efficacy, patient compliance, and superiority over conventional topical formulations in the management of chronic dermatological conditions such as psoriasis, eczema, acne vulgaris, fungal infections, and skin cancer. Although numerous preclinical studies have demonstrated promising outcomes, successful clinical translation requires robust evidence from multicenter human studies. Simultaneously, there is a pressing need to develop scalable, cost-effective, and reproducible manufacturing processes that ensure batch to batch consistency, high encapsulation efficiency, and long term stability while meeting regulatory and industrial standards for commercialization. Future investigations should also explore combination therapies in which bilosomes co-deliver multiple therapeutic agents, including conventional drugs, phytochemicals, peptides, nucleic acids, or immunomodulators, to achieve synergistic therapeutic effects, minimize drug resistance, and reduce treatment related adverse effects. Another promising direction involves the development of surface functionalized bilosomes by incorporating ligands, antibodies, peptides, or polymers that enable targeted delivery to specific skin cells, hair follicles, inflamed tissues, or tumor microenvironments, thereby improving therapeutic precision and minimizing off target effects. Furthermore, the design of stimuli-responsive bilosomal systems capable of releasing their drug payload in response to physiological or external triggers such as pH, temperature, enzymes, reactive oxygen species, light, ultrasound, or magnetic fields represents an innovative strategy for achieving controlled and site specific drug delivery. Finally, integrating bilosomal formulations with advanced drug delivery platforms, including hydrogels, dissolving microneedles, nanofiber mats, wound dressings and three-dimensional (3D)-printed topical dosage forms, has the potential to enhance skin penetration, prolong drug residence time, improve patient adherence, and facilitate personalized treatment approaches. Collectively, these research directions are expected to accelerate the clinical translation of bilosomal technology and establish it as a versatile, effective, and commercially viable platform for the treatment of a wide range of skin diseases. These advances may facilitate the translation of bilosomal formulations into clinically approved therapies.

CONCLUSION

Bilosomes represent an advanced lipid based nanocarrier with significant potential for improving topical drug delivery in various skin diseases. Their enhanced flexibility, stability, and ability to penetrate the stratum corneum make them superior to conventional liposomes for dermal applications. Preclinical studies have demonstrated encouraging results in psoriasis, acne, fungal infections, bacterial skin diseases, atopic dermatitis, and skin cancer. Furthermore, the growing number of patents related to bilosomal formulations, novel lipid compositions, bile salt incorporation, targeted delivery approaches, and sustained release topical systems reflects increasing industrial interest and commercial potential. These patent developments provide valuable intellectual property protection and are expected to accelerate the translation of bilosomes based technologies into clinically viable dermatological products. However, additional clinical studies, standardized manufacturing methods, and clear regulatory guidance are essential to support their successful translation into routine dermatological practice.

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