Design and development of niacinamide lipid and polymeric nanoparticles and in vitro permeation studies using human epidermis

Abstract

Niacinamide (NIAC), also known as nicotinamide, is a Biopharmaceutics Classification System (BCS) Class I compound with versatile known dermatological benefits, including anti-inflammatory, antioxidant, brightening, and skin barrier-restoring effects. However, due to its high hydrophilicity and the barrier properties of the stratum corneum, it is characterized by poor skin permeation. This study aimed to develop both lipid and polymer nanoparticles and comparatively assess their potential for the enhancement of NIAC delivery through the skin. Lipid nanoparticles composed of hydrogenated soy phosphatidylcholine (HSPC) and phosphatidylglycerol (PG) were prepared via a simple thin-film hydration method. A two-factor (3²) factorial experimental design was used to determine the effects of PG and colloidal concentration (CollC) on physicochemical properties: hydrodynamic diameter (D_h), polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE) of NIAC, as well as to optimize the lipid formulation. The presence of PG ameliorated physicochemical characteristics and increased NIAC encapsulation up to 56%. Two of five optimized formulations were further investigated for in vitro permeation across human epidermis using Franz diffusion cells, with a non-optimized formulation and a 4.5% NIAC solution used as references. Optimized LNPs substantially enhanced skin permeation; compared with the non-optimized formulation, they improved permeation by 39% and overall delivery by 22%. Compared with the 4.5% NIAC solution, they exhibited 192% greater permeation and 800% higher overall delivery efficiency. These findings demonstrate the potential of PG-containing LNPs as effective nanocarriers for cosmetic or dermatological applications. In parallel, polymeric nanoparticles based on Kolliphor® P407 were prepared by bath sonication as an alternative delivery platform for niacinamide, where the influence of the polymer and compound concentrations was examined. Interestingly, the formulation with the minimum total concentration (10 mg mL⁻¹, 9 : 1 polymer : NIAC ratio) displayed the best overall performance, achieving a balance of colloidal stability, micellar homogeneity, and release capacity. Overall, polymeric nanoparticles yielded interesting delivery profiles for the hydrophilic molecule and appeared to facilitate its permeation through the skin, despite the rather limited NIAC encapsulation efficiency achieved; their potential remains to be elucidated more extensively.