Three-Dimensional Printing Technologies for Drug Delivery Applications: Processes, Materials, and Effects.

Since the 1930s, new methods of drug delivery, such as implantable devices with drug release control, have been developed. However, manufacturing techniques require bulk due to high initial production costs. Three-dimensional (3D) printing, also known as additive manufacturing or rapid prototyping, allows the fabrication of personalized drug delivery that uses different materials and complex geometries with multiple release profiles, thereby eradicating high initial costs. Different studies have been developed showing the extensive potential of 3D printing for the pharmaceutical industry, and despite in-depth discussions that have been published, there is no comprehensive review of processes, materials, and effects in drug delivery applications thus far. This review aims to fill this gap by presenting the use of 3D printing technology for drug delivery, exposing the different variations of the technique according to the characteristics, material, and dosage form sought. There are seven main categories of 3D printing according to the standards jointly developed by International Organization for Standardization and American Society for Testing and Materials: material jetting, binder jetting, material extrusion, vat photopolymerization, powder bed fusion, sheet lamination, and directed energy deposition. There are different 3D fabrication processes used for drug delivery applications depending on the dosage form and material applied. In this context, polymers, glasses, and hydrogels represent the most frequent materials used. 3D printing allows different forms of drug dosage. Oral, topical, rectal and vaginal, parental and implantable are discussed in this paper, presenting the identification of the type of 3D printing technology, the active pharmaceutical ingredient, formulation, and pharmaceutical effect. The main aim of this paper is to offer insights to people from academy and industry who are interested in the advancement of drug delivery and in knowing the future directions in the development of 3D printing applications in this area.

Analysis of 1,25-Dihydroxyvitamin D3 Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids.

Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-activated genes in the proximal intestine associated with active calcium transport (Trpv6, S100g, and Atp2b1) are also induced by 1,25(OH)2D3 in the distal intestine of KO/TG mice. In addition, Slc30a10, encoding a manganese efflux transporter, was one of the genes most induced by 1,25(OH)2D3 in both proximal and distal intestine. Both villus and crypt were found to express Vdr and VDR target genes. RNA sequence (RNA-seq) analysis of human enteroids indicated that the effects of 1,25(OH)2D3 observed in mice are conserved in humans. Using Slc30a10-/- mice, a loss of cortical bone and a marked decrease in S100g and Trpv6 in the intestine was observed. Our findings suggest an interrelationship between vitamin D and intestinal Mn efflux and indicate the importance of distal intestinal segments to vitamin D action.

Vitamin D and the intestine: Review and update.

The central role of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. This article describes the early work that served as the foundation for the initial model of vitamin D mediated calcium absorption. In addition, other research related to the role of vitamin D in the intestine, including those which have challenged the traditional model and the crucial role of specific calcium transport proteins, are reviewed. More recent work identifying novel targets of 1,25(OH)2D3 action in the intestine and highlighting the importance of 1,25(OH)2D3 action across the proximal/distal and crypt/villus axes in the intestine is summarized.

New developments in our understanding of vitamin metabolism, action and treatment.

Although vitamin D has been reported to have pleiotropic effects including effects on the immune system and on cancer progression, the principal action of vitamin D is the maintenance of calcium and phosphate homeostasis. The importance of vitamin D in this process is emphasized by the consequences of vitamin D deficiency which includes rickets in children and osteomalacia in adults. Vitamin D deficiency has also been reported to increase the risk of falls and osteoporotic fractures. Although vitamin D fortification of foods (including dairy products) has contributed to a marked decrease in rickets in the Western world, vitamin D deficiency in children and adults is still prevalent world-wide. This review summarizes new developments in our understanding of vitamin D endocrine system and addresses clinical syndromes related to abnormalities in vitamin D metabolism and action. In addition, the current understanding of the evaluation of vitamin D deficiency and sufficiency and recommendations for achieving vitamin D sufficiency are discussed.