Design of Experiments in the Formulation and Characterization of 3D-Printed Vaginal Films Loaded with Curcumin Solid Lipid Nanoparticles for Cervical Dysplasia

TL;DR

This paper introduces a new 3D-printed vaginal film containing curcumin nanoparticles to treat cervical dysplasia, offering a non-invasive alternative to surgery.

Contribution

The novel contribution is the development of a self-administered, curcumin-loaded nanoparticle film for localized treatment of cervical dysplasia.

Findings

Curcumin solid lipid nanoparticles showed enhanced cell mortality and autophagosome formation in cervical cancer cells.

The nanoparticles significantly increased immune cell surface markers compared to free curcumin.

Optimized film properties include rapid disintegration and sustained curcumin release.

Abstract

Background/Objectives: Cervical dysplasia, a precursor to cervical cancer, represents a significant global health challenge, particularly in regions like Central America, Africa, and Southeast Asia. Current management approaches rely on surgical or ablative interventions, which can lead to complications, for example, preterm birth and cervical insufficiency. Therefore, developing non-invasive, localized therapeutic alternatives is of great clinical interest. Curcumin is a natural compound that suppresses the progression of cervical cancer, but it has poor oral bioavailability and high clearance. Methods: We incorporated curcumin into solid lipid nanoparticles, which were then loaded into rapidly dissolving films. These films show the sustained release profile of curcumin at the localized vaginal site, demonstrating release kinetics consistent with the Korsmeyer–Peppas model. Results: The curcumin solid lipid nanoparticles yielded a size of 341 nm and a polydispersity index of 0.373, and the zeta potential was −23.4 mV. The encapsulation efficiency of curcumin solid lipid nanoparticles was 77.27% using a validated HPLC method. FTIR analysis supported successful incorporation of curcumin into the lipid matrix. A Box–Behnken Design of Experiments optimized the key film formulation parameters and yielded a film with a tensile strength of 2.8 mPa, disintegration time of 3 min, folding endurance of 263, film thickness of 0.426 mm and a pH of 4.0. Conclusions: In vitro assays in human cervical carcinoma cells demonstrated enhanced mortality and autophagosome formation by the curcumin solid lipid nanoparticles when compared to free curcumin. Surface expression of MHC I, MHCII, CD40 and CD80 in peripheral dendritic cells was significantly higher in the curcumin solid lipid nanoparticles than in free curcumin. Results show that solid lipid nanoparticles loaded with curcumin effectively stimulate and activate dendritic cells, supporting immune cell activation outside the tumor microenvironment. The proposed pain-free self-administration strategies will lead to increased patient compliance.

Figures