**3. Conclusion**

Almouazen and partners encapsulated calcidiol in poly‐lactic acid (PLA) nanoparticles to ensure specific action on malignant cells avoiding side effects as hypercalcemia. The authors developed nanocapsules with about 200 nm of mean diameter. Cellular studies showed a significant growth inhibition when calcidiol was entrapped in the PLA nanocapsules, when compared to free calcidiol, proving that the nanocarrier enhanced the intracellular delivery of vitamin D on breast cancer cells. The attained results showed that PLA nanocapsules are a

Bonor and coworkers developed calcitriol‐conjugated quantum dots to study the distribution of calcitriol in mouse cancer cells. The designed tool is suitable for imaging drug‐tumor

Ignjatović and colleagues prepared hydroxyapatite (Hap) and PLGA‐based nanoparticles for the local delivery of VD to enhance osteogenesis and bone tissue differentiation. The attained NPs exhibited mean diameters of 100 nm and a biphasic release profile. *In vitro* biocompati‐ bility studies were conducted using osteoblastic cells. In animal studies, the authors verified that osteogenesis and bone structure differentiation were enhanced when VD was delivered

Ramalho and colleagues developed PLGA nanoparticles for the delivery of calcitriol for an antitumor therapy application. Initially, the authors used cholecalciferol as drug model for calcitriol to assess the influence of several experimental conditions, such as sonication time and VD/polymer ratio, on the NPs physicochemical properties. After achieving the optimized experimental conditions, the group synthesized calcitriol‐loaded PLGA NPs with spherical form and mean diameters smaller than 200 nm as shown in **Figure 6**, and stable for several weeks at storage conditions (4°C). The attained nanosystems exhibited encapsulation efficien‐ cy values of approximately 60%. The prepared PLGA NPs exhibited a biphasic release profile, with an initial burst release in the first 24 h, followed by a slower and controlled release for 7 days. Human cancer cell lines were used to evaluate the toxicity of VD‐loaded PLGA NPs. The obtained nanoparticles formulation was successfully internalized by the target cells and enhanced the vitamin's antitumor effect, showing a clear efficacy in the therapeutic effects as

**Figure 6.** TEM images: (a) unloaded PLGA nanospheres; scale bar: 200 nm; (b) VD‐loaded PLGA nanospheres; scale

These developed systems reported in the literature allowed maintaining active doses of VD for long periods of time, due to their controlled and sustained release. These nanosystems also

suitable choice for the controlled delivery of calcidiol [13].

cell cycle arrest and major changes in cell's morphology [30].

by the developed system [46].

244 A Critical Evaluation of Vitamin D - Clinical Overview

bar: 500 nm [30].

interactions and to deliver drugs to tumors and metastasized sites [45].

With the growing awareness of vitamin D health benefits, as well of the harmful risks associ‐ ated to vitamin D insufficiency, finding new solutions has become urgent within the scientific community. In more recent years, nanotechnology has emerged as a suitable answer to these issues, allowing to take advantage of the beneficial effects of this micronutrient, while over‐ coming some of the disadvantages associated with its administration. Nanoparticles provide protection from external conditions, and increase the stability and solubility of the molecule. Also, nanoparticles allow decreasing its toxicity associated with the hypercalcemia phenom‐ ena, and allowing circumventing the multidrug resistance problem hindering the molecule efflux out of the cells. Only a few nanosystems have been described for different applications, such as food and beverage fortification and as therapeutic agents, as shown in this chapter. It would be essential to conduct more substantial and insightful studies to support the great potential of nanotechnology for the delivery of vitamin D. Also, it would be valuable to optimize the already‐described systems to make them more efficient and specific to a specific target tissue.
