Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization.

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.

Inhalable Jojoba Oil Dry Nanoemulsion Powders for the Treatment of Lipopolysaccharide- or H2O2-Induced Acute Lung Injury.

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (H2O2). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on H2O2-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or H2O2-induced ALI.

Amifostine-loaded armored dissolving microneedles for long-term prevention of ionizing radiation-induced injury.

Amifostine is a cytoprotective agent against the hematopoietic damage induced by ionizing radiation, although the intravenous injection of amifostine is a unique administration method with strict dosing time limitation. Hence, the fields of application of amifostine are greatly limited. Here, we developed an amifostine-loaded armored microneedle (AAMN) with long-term prevention of hematopoietic injury induced by ionizing radiation. First, amifostine-loaded hyaluronic acid microneedles (AMNs) were fabricated, and the AMNs were then dipped in an N-vinyl-2-pyrrolidone (NVP) solution followed by ultraviolet (UV) photocuring to obtain AAMNs. AAMNs were nail-shaped with much higher mechanical strength compared to the conical shape and weak strength of AMNs, which was verified by their in silico simulation. In the in vitro release experiment, more than 55% of amifostine was released from AAMNs within 10 min, and 95% was released in 60 min. Drug skin permeation of AAMNs was also high, at twice that of AMNs. AAMNs provided long-term protection of the hematopoietic system from radiation within 3-7 h pre-radiation compared to the unique amifostine injection 0.5 h pre-radiation because topical application of AAMNs led to the long-term maintenance of the in vivo effective drug concentration. More importantly, AAMNs led to the survival of all irradiated mice due to intravenous amifostine. AAMNs are a promising transdermal delivery system of amifostine for long-term protection against ionizing radiation-induced injury. STATEMENT OF SIGNIFICANCE: An amifostine-loaded dissolving armored microneedle (AAMN) patch is developed for long-term prevention of ionizing radiation-induced injury. High drug loads in microneedles (MNs) with adequate mechanical strength is a challenge. We fabricated armors on the surface of high amifostine-loaded hyaluronic acid microneedles (AMNs) by dipping the tips of AMNs in N-vinyl-2-pyrrolidone (NVP) solutions and then subjecting them to UV irradiation, and high-strength armored AMNs (AAMNs) were obtained. AAMNs show deeper skin insertion and much higher drug permeation than AMNs. The controlled drug release from AAMNs in the mouse skins provides a long-term protection of radiation-induced injury with 3-7 h administration pre-radiation compared to the merely 0.5-h point of amifostine injection.

3D printed mold-based capsaicin candy for the treatment of oral ulcer.

Oral ulcer is one common mucosal disease with high prevalence. Here, capsaicin candies were prepared based on the stereolithographically (SLA) 3D printed molds. The molds can be freely designed depending on the needs of patients, involving symmetric shapes (e.g., round, four-lead clover and cube), asymmetric shapes (e.g., car) and various color (e.g., blue, red and yellow). A two-part-combined mold was filled with the xylitol-based material and separated to obtain hard candies. Capsaicin was amorphous in the candies according to the differential scanning calorimetry and X-ray diffraction. Poloxamer 188 improved the release of capsaicin from the candies. Rat oral ulcer models were established on the tongue with phenol liquids. The blank candy, 0.05% capsaicin candy and dexamethasone were respectively administered on the ulcer once daily. On Day 7, a healing rate of 97.8% was achieved by the capsaicin candy, much higher than those in the other groups. Moreover, the blank candy also showed the remarkable ulcer healing effect due to the presence of xylitol and poloxamer. Capsaicin remarkably enhanced the reepithelialization of ulcer tissues and showed strong anti-inflammatory effect by reducing the expressions of THF-α and IL-6. 3D printing-based capsaicin candies provide an interesting therapeutic choice for the people with oral ulcer.