Mucoadhesive CR8L10@CAT nano-formulation effectively treats interstitial cystitis and acute lung injury.

Mucosal inflammatory diseases, such as interstitial cystitis/bladder pain syndrome (IC/BPS) and acute lung injury (ALI), are often driven by excessive reactive oxygen species (ROS) burden in the microenvironment. Current therapeutic approaches struggle with poor drug retention due to physiological clearance mechanisms, limiting efficacy. This necessitates novel drug delivery strategies that can specifically target and adhere to inflamed mucosal regions. Developing mucoadhesive antioxidant formulations offers a promising avenue to overcome these challenges, ensuring sustained therapeutic action where it's needed most.

Researchers developed a covalent mucoadhesive nanoantioxidant, CR8L10@CAT, self-assembled from a cysteine-modified short peptide (CR8L10) and catalase (CAT). The CR8L10@CAT nanocomplexes were evaluated for their ability to treat mucosal inflammatory diseases. For IC/BPS, the formulation was administered via intravesical instillation, assessing bladder retention and therapeutic effects. For ALI, the CR8L10@CAT nanoantioxidant was delivered via inhalation. Efficacy was determined by measuring ROS elimination, pro-inflammatory responses, urothelial integrity, pain alleviation, and voiding dysfunction, comparing against clinically used intravesical agents.

The CR8L10@CAT nanocomplexes, featuring a cysteine-decorated surface, demonstrated robust mucoadhesion by forming dynamic disulfide bonds with mucin-rich mucosa, leading to significantly enhanced catalase retention. Upon intravesical instillation, CR8L10@CAT exhibited improved urine-resistant bladder retention. This enhanced retention allowed for effective elimination of excessive ROS in the bladder mucosa, thereby inhibiting pro-inflammatory responses. The treatment also restored urothelial integrity and alleviated pain and voiding dysfunction in models of IC/BPS.

Notably, CR8L10@CAT showed significantly better analgesic effects and superior functional improvement than clinically used intravesical agents. Additionally, inhalation of the mucoadhesive CR8L10@CAT nanoantioxidant resulted in enhanced pulmonary retention, effectively mitigating ROS-associated inflammation in models of ALI.