Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study.

CONTEXT: The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications. METHODS: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion. RESULTS: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.

Hard and soft tissue evaluation of alveolar ridge preservation compared to spontaneous healing: a retrospective clinical and volumetric analysis.

PURPOSE: The remodeling process following tooth extraction can be observed as horizontal and vertical bone reduction of the alveolar ridge. Preservation procedures such as alveolar ridge preservation (ARP) aim to maintain the 3D volume of the extraction site. This retrospective study analyzed differences in the hard and soft tissue changes in patients treated with either spontaneous healing or ARP. METHODS: After tooth extraction, the patients were treated either by spontaneous socket healing (SH group) or with ARP using a xenograft and a resorbable membrane (ARP group). One week before and 6 months after extraction, the patients underwent cone beam computed tomography. A volumetric analysis was performed by superimposing the digital models of the two time points. Intraoral radiography was performed after implant placement, upon prosthesis delivery, and at 1-year post-treatment. An esthetic assessment was conducted using the Pink Esthetic Score (PES). The patients' overall satisfaction with the implant restoration was investigated at 12 months. RESULTS: Intragroup comparisons revealed significant differences between baseline and the 6-month follow-up in both groups at the measured locations (1 mm, 3 mm, and 5 mm below the most coronal aspect of the alveolar ridge) showing a reduction of the horizontal width (P < 0.05). Additionally, after treatment, the horizontal width at 1 mm was significantly different in the SH and ARP groups (P < 0.001), with mean changes of 2.03 ± 0.54 mm and 0.86 ± 0.49 mm, respectively. ARP was associated with an increased PES (11.6 ± 2.2) and a reduction in patients requiring additional grafting procedures in subsequent treatment phases (9% vs 26%; P = 0.11). CONCLUSIONS: In both groups, significant horizontal and vertical bone loss was observed after the extraction. ARP can reduce linear and volumetric shrinkage of the alveolar ridge, leading to improved outcomes. It can also simplify implant restoration.