Optimization of Curcumin Nanocrystals as Promising Strategy for Nose-to-Brain Delivery Application

Abstract

Intranasal (IN) drug delivery is recognized to be an innovative strategy to deliver drugs to the Central Nervous System. One of the main limitations of IN dosing is the low volume of drug that can be administered. Accordingly, two requirements are necessary: the drug should be active at a low dosage, and the drug solubility in water must be high enough to accommodate the required dose. Drug nanocrystals may overcome these limitations; thus, curcumin was selected as a model drug to prepare nanocrystals for potential IN administration. With this aim, we designed curcumin nanocrystals (NCs) by using Box Behnken design. A total of 51 formulations were prepared by the sonoprecipitation method. Once we assessed the influence of the independent variables on nanocrystals’ mean diameter, the formulation was optimized based on the desirability function. The optimized formulation was characterized from a physico-chemical point of view to evaluate the mean size, zeta potential, polidispersity index, pH, osmolarity, morphology, thermotropic behavior and the degree of crystallinity. Finally, the cellular uptake of curcumin and curcumin NCs was evaluated on Olfactory Ensheathing Cells (OECs). Our results showed that the OECs efficiently took up the NCs compared to the free curcumin, showing that NCs can ameliorate drug permeability.

Curcumin Loaded Polymeric vs. Lipid Nanoparticles: Antioxidant Effect on Normal and Hypoxic Olfactory Ensheathing Cells

“…However, this route presents some disadvantages due to the site of administration, in fact, when the drug molecule enters into the nasal cavity, it experiences mucociliary clearance in the vestibular region which restricts foreign particles and the potential local drug enzymatic degradation. Moreover, it is suitable only for potent drugs since a limited volume (100–200 µL) can be sprayed into the nasal cavity [ 4 , 5 ]. On the other hand, nanomedicine, over the last two decades, has been growing quickly and it is used in disease diagnosis and treatment to overcome some pharmacokinetic limits [ 6 ].…”

Curcumin nanonization using an alternative small-scale production unit: selection of proper stabilizer applying basic physicochemical consideration and biological activity assessment of nanocrystals

“…It should be underlined that many research publications dealt with curcumin nanocrystals in terms of preparation method and physical aspects [26,28,30,[42][43][44]. However, little has been done to evaluate the biological performances of this pleiotropic molecule after the processing, even though its susceptibility to physicochemical degradation is well known.…”

Chronic Inflammatory Diseases, Anti-Inflammatory Agents and Their Delivery Nanosystems

“…For these reasons, its therapeutic use in medicine is limited, but great efforts have been made for a long time to investigate suitable usable nanoformulations [ 153 , 154 , 155 ]. Due to the huge number of such described nanoformulations (e.g., Figure 5 ), the overview of which would require a separate paper, only a few reviews or recently published important articles are listed here [ 78 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 ]. For example, Coradini et al [ 165 ] formulated CUR and resveratrol into lipid core nanocapsules.…”