Redispersible 3D printed nanomedicines: An original application of the semisolid extrusion technique.

Semisolid extrusion is a layer-by-layer 3D printing technique that produces objects from gels or pastes. This process can be carried out at room temperature, without using a light source, and has been explored in pharmaceutics in the last few years. In this regard, our group hypothesized its suitability for the production of three-dimensional (3D) printed nanomedicines containing drug-loaded organic nanocarriers. In this study, the original application of the semisolid extrusion was evaluated to produce redispersible 3D printed oral solid forms containing drug-loaded polymeric nanocapsules. A carboxymethyl cellulose hydrogel containing resveratrol and curcumin co-encapsulated in nanocapsules was prepared, and the nanocapsules did not change its complex viscosity and yield stress. Homogeneous and yellow cylindrical-shaped solid forms were printed, with a mean weight of 0.102 ± 0.015 g, a polyphenol content of approximately 160 µg/unit, disintegration time of <45 min, and recovery of the nanosized carriers. The polyphenols were completely released from the solid forms after 8 h, although part of them remained encapsulated in the nanocapsules. This study represents a proof of concept concerning the use of semisolid extrusion to produce 3D printed forms composed of polymeric nanocapsules in a one-step process. It proposes an original platform for the development of solid nanomedicines from liquid aqueous nanocapsule suspensions.

Drug-loaded mesoporous silica on carboxymethyl cellulose hydrogel: Development of innovative 3D printed hydrophilic films.

3D printing has been explored as an emerging technology for the development of versatile and printable materials for drug delivery. However, the alliance of 3D printing and nanomaterials has, to date, been little explored in pharmaceutics. Herein, a mesoporous silica with nanostructured pores, SBA-15, was used as a drug carrier for triamcinolone acetonide, a hydrophobic drug, with the aim of incorporating the drug formulation in a hydrophilic printable ink. The adsorption of the drug in the SBA-15 pores was confirmed by the decrease in its surface area and pore volume, along with an increase in the apparent aqueous solubility of triamcinolone acetonide, as shown by in vitro release studies. Thereafter, a hydrophilic ink composed of carboxymethyl cellulose containing drug-loaded SBA-15 was formulated and 3D printed as hydrophilic polymeric film using the semisolid extrusion technique (SSE). The 3D printed films showed complete drug release after 12 h, and the presence of the triamcinolone acetonide-loaded SBA-15 improved their in vitro mucoadhesion, suggesting their promising application in oral mucosa treatments. Besides representing an innovative platform to develop water-based mucoadhesive formulations containing a hydrophobic drug, this is the first report proposing the development of SSE 3D printed nanomedicines containing drug-loaded mesoporous silica.

Bioadhesive 3D-Printed Skin Drug Delivery Polymeric Films: From the Drug Loading in Mesoporous Silica to the Manufacturing Process.

The alliance between 3D printing and nanomaterials brings versatile properties to pharmaceuticals, but few studies have explored this approach in the development of skin delivery formulations. In this study, clobetasol propionate (CP) was loaded (about 25% w/w) in mesoporous silica nanomaterial (MSN) to formulate novel bioadhesive and hydrophilic skin delivery films composed of pectin (5% w/v) and carboxymethylcellulose (5% w/v) by 3D printing. As a hydrophobic model drug, CP was encapsulated in MSN at a 3:1 (w/w) ratio, resulting in a decrease of CP crystallinity and an increase of its dissolution efficiency after 72 h (65.70 ± 6.52%) as compared to CP dispersion (40.79 ± 4.75%), explained by its partial change to an amorphous form. The CP-loaded MSN was incorporated in an innovative hydrophilic 3D-printable ink composed of carboxymethylcellulose and pectin (1:1, w/w), which showed high tensile strength (3.613 ± 0.38 N, a homogenous drug dose (0.48 ± 0.032 mg/g per film) and complete CP release after 10 h. Moreover, the presence of pectin in the ink increased the skin adhesion of the films (work of adhesion of 782 ± 105 mN·mm). Therefore, the alliance between MSN and the novel printable ink composed of carboxymethylcellulose and pectin represents a new platform for the production of 3D-printed bioadhesive films, opening a new era in the development of skin delivery systems.