Recent Developments in Invasomal Drug Delivery Systems for Effective Topical Therapy: A Review

Abstract

ABSTARCTCutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skincancer (NMSC), with topical therapies offering a promising opportunity for treatment; however,their delivery to target tissues is often inadequate. Invasive phospholipid nanovesicles enrichedwith both ethanol and terpenes (Invasomes) were developed as a tailorable, disruptivetranslational platform towards precision topical drug delivery. Invasomes improve dermalpenetration of chemotherapeutics (i.e. tretinoin, 5-fluorouracil and resveratrol) by fluidizing andreorganizing stratum corneum lipids which allow high local drug deposition in tumor-bearingepidermal and superficial dermal layers with reduced systemic exposure.The authors distinguishthe structural design and compositional construction of invasomes, which include keyphospholipids (i.e.phosphatidylcholine) and performance determining terpenes (menthol,limonene), and describe their synergistic mechanisms that support superior skin retention,sustained release and enhanced bioavailability as compared to other conventional vesicularsystems (i.e. liposomes and ethosomes). Advanced manufacture strategies including thin-filmhydration, mechanical dispersion, reverse-phase evaporation, and ether injection are criticallyassessed in relation to vesicle size (≈200 nm), entrapment efficiency (>75%), and colloidalstability along with scalability for further development. Beyond CSCC, invasomes are expectedto have a wide range of applications in the treatment of psoriasis, infectious dermatoses,neglected tropical dermal diseases, and wound healing along with preclinical data and patentapplications stating 3-4 times improvements in cutaneous permeation and robustpharmacodynamics. Formulation induced irritation, along with vesicle aggregation and long termstability, remains the greatest challenges. These are addressed through the use of cryoprotectants,surface engineering, and lyophilization as stabilization strategies. The article also discusses theuse of stimuli-responsive systems, excited hybrid invasome systems and aim-guided formulationstrategies to optimize invasomes with the aim of creating a dermal nanotherapeutic for highlytargeted skin cancer treatments.