02595nas a2200217   4500000000100000008004100001260001200042653001400054653002100068653001400089653001400103653001300117653001800130100001600148700001200164700001900176700001200195245013200207520202400339022001402363       2025                            d  c11/202510aCerosomes10aCo-encapsulation10aEthosomes10aLiposomes10aNiosomes10aSkin delivery1 aRodrigues S1 aVeiga F1 aPaiva-Santos A1 aPires P00aDual drug co-encapsulation into liposomes and liposome-derived nanosystems for improved synergistic treatment of skin diseases.3 a<p>Skin disorders impact nearly one-third of the global population, and represent the fourth most common cause of human diseases. However, delivering drugs into and through the skin is a significant challenge due to its low permeability, which severely limits the efficacy of conventional topical and transdermal formulations. To tackle this issue, liposomes and liposome-derived nanosystems can be of use, which, among other advantages, also have the capacity to encapsulate more than one drug molecule simultaneously, allowing combination therapy. This review provides a comprehensive summary and critical analysis of recent studies regarding dual drug co-encapsulation into liposomes and liposome-derived nanosystems as an improved therapeutic approach for the treatment of several skin diseases, such as acne vulgaris, androgenetic alopecia, cutaneous leishmaniasis, psoriasis, vitiligo, and chronic wounds, and for dermal analgesia and general skin oxidative stress management purposes. Conventional and modified liposomes, niosomes, transfersomes, ethosomes, invasomes, cerosomes, liposomal gels, and niosomal gels were developed, co-encapsulating synthetic and nature-derived substances such as adapalene, amphotericin B, benzoyl peroxide, bicalutamide, bupivacaine, buprenorphine, curcumin, ginger, glycyrrhetinic acid, metformin, methotrexate, microRNA-21, minoxidil, nicotinamide, Nigella sativa seed oil, pentamidine, psoralen, resveratrol, simvastatin, tocopherol acetate, tretinoin, and virgin coconut oil. By co-encapsulating active substances with distinct mechanisms of action, the developed nanosystems provide synergistic therapeutic effects, leading to reduced toxicity and enhanced bioavailability, potentially resulting in improved clinical outcomes, and presenting a promising alternative to conventional treatments. Through addressing clinical and regulatory framework aspects, these innovative therapies might one day transition from bench to market to improve the patient's quality-of-life.</p>  a2190-3948