Three-dimensional (3D) printers have been applied in many fields, including engineering and the medical sciences. In the pharmaceutical field, approval of the first 3D-printed tablet by the U.S. Food ...and Drug Administration in 2015 has attracted interest in the manufacture of tablets and drugs by 3D printing techniques as a means of delivering tailor-made drugs in the future. In current study, polyvinylalcohol (PVA)-based tablets were prepared using a fused-deposition-modeling-type 3D printer and the effect of 3D printing conditions on tablet production was investigated. Curcumin, a model drug/fluorescent marker, was loaded into PVA-filament. We found that several printing parameters, such as the rate of extruding PVA (flow rate), can affect the formability of the resulting PVA-tablets. The 3D-printing temperature is controlled by heating the print nozzle and was shown to affect the color of the tablets and their curcumin content. PVA-based infilled tablets with different densities were prepared by changing the fill density as a printing parameter. Tablets with lower fill density floated in an aqueous solution and their curcumin content tended to dissolve faster. These findings will be useful in developing drug-loaded PVA-based 3D objects and other polymer-based articles prepared using fused-deposition-modeling-type 3D printers.
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A unique two-solution mixing-type spray nozzle is useful for producing nanocomposite particles (microparticles containing drug nanoparticles) in one step. The nanocomposite particles ...can prevent nanoparticle aggregation. Curcumin has many reported pharmacological effects. Curcumin was entrapped in mannitol microparticles using a spray dryer coupled with a two-solution mixing-type spray nozzle to prepare ⿿curcumin nanocomposite particles⿿ and the application of these particles for inhalation formulations was investigated. Spray drying conditions (flow rate, concentration and inlet temperature) affected the size of both the resulting curcumin nanocomposite particles and the curcumin nanoparticles in the nanocomposite particles. The aerosol performance of the curcumin nanocomposite particles changed depending on the spray drying conditions and several conditions provided better deposition compared with the curcumin original powder. The curcumin nanocomposite particles showed an improved dissolution profile of curcumin compared with the original powder. Furthermore, the curcumin nanocomposite particles showed a higher cytotoxic effect compared with the curcumin original powder towards three cancer cell lines. Curcumin nanocomposite particles containing curcumin nanoparticles show promise as an inhalation formulation for treating lung-related diseases including cancer.
Gold nanoparticles (GNPs) have promising properties such as photothermal effects and could be useful for imaging and as multifunctional nanocarriers for various drugs. In this study, we synthesized ...polyethyleneglycol (PEG)-grafted GNPs and conjugated them with cyclodextrin (CD) to incorporate curcumin. Curcumin has anticancer effects but its therapeutic application is limited due to poor water solubility. Three types of CDs (α-, β-, and γ-CDs) were conjugated with PEGylated GNPs and the curcumin-containing CD/PEG-conjugated GNPs (cur-CD-GNPs) were characterized. Transmission electron microscopy and dynamic light scattering results showed that these cur-CD-GNPs have a small gold nanocore (approximately 5 nm) and the average size of the three cur-CD-GNPs was approximately 25–35 nm. Curcumin was efficiently incorporated into the β-CD solution and the loading efficiency of curcumin in β-CD-GNPs was the highest of the three types of CD-GNPs prepared. The cytotoxic effect of cur-CD-GNPs was investigated using a human lung cancer cell line. All cur-CD-GNPs exhibited cytotoxic effects comparable to that of curcumin solution and CD-GNPs without curcumin were not cytotoxic. These results suggest that cur-CD-GNPs may be a useful multifunctional nanomedicine, although in vivo investigations are required.
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3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a ...fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers.
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The liposome–protamine–DNA complex (LPD) is an effective cationic carrier of various nucleic acid constructs such as plasmid DNA and small interfering RNA (siRNA). Hyaluronic acid ...coated on LPD (LPDH) reduces cytotoxicity and maintains the silencing effect of LPD-encapsulated siRNA. Herein, we aim to develop LPD- or LPDH-containing spray-freeze-dried particles (SFDPs) for therapeutic delivery of siRNA to the lungs. LPD- or LPDH-containing SFDPs (LPD- or LPDH-SFDPs) were synthesized and their structure and function as gene carriers were evaluated using physical and biological methods. The particle size of LPDH, but not of LPD, was constant after re-dispersal from the SFDPs and the amount of siRNA encapsulated in LPDH was larger than that in LPD after re-dispersal from the SFDPs. The in vitro pulmonary inhalation properties of LPDH-SFDPs and LPD-SFDPs were almost the same. The cytotoxicity of LPDH-SFDPs in human umbilical vein endothelial cells (HUVEC) was greatly decreased compared with that of LPD-SFDPs. In addition, Bcl-2 siRNA in LPDH-SFDPs had a significant gene silencing effect in human lung cancer cells (A549), whereas Bcl-2 siRNA in LPD-SFDPs had little effect. These results indicate that compared with LPD, LPDH is more useful for developing SFDPs for siRNA pulmonary inhalation.
We maintained the function of an extracted rat heart after 24-48 h preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O
). Here, we assessed the effects of different ...partial pressures of hyperbaric CO and O
for 24-48 h at 4 °C on rat heart preservation and compared conditions including immersion in University of Wisconsin solution. Preserved hearts were transplanted into recipient rats via heterotopic cervical heart transplantation for in vivo evaluation and perfused using the Langendorff system for ex vivo evaluation. The survival rate of transplanted hearts was 100% at postoperative day 7 in the CO + O
(PCO:PO
= 1.5:2.0 atm) group but only 33% in the CO + O
(PCO:PO
= 2.0:1.5 atm) group. Langendorff system and histopathological analysis revealed that the left ventricular pressure of preserved hearts in the CO + O
(PCO:PO
= 1.5:2.0 atm) group was better than the CO + O
(PCO:PO
= 2.0:1.5 atm). We demonstrate that exposure of rat hearts to hyperbaric CO and O
is superior to the immersion method and that partial pressure of hyperbaric CO and O
is crucial to preservation.
Objective
Acute limb ischemia (ALI) is a rapid decrease in lower limb blood flow due to acute occlusion of peripheral arteries or bypass grafts. This study aimed to establish an ALI model using ...microsized gelatin beads and to investigate the pathophysiological conditions.
Methods
Male Sprague-Dawley rats were anesthetized, and a low or high dose of microsized gelatin beads was administered into the left femoral artery on days 0 and 7. A control, that is, normal saline (NS) group in which NS was administered in the left femoral artery, a femoral artery cut (FAC) group in which the left femoral artery was cut, and a sciatic nerve cut (SNC) group in which the left sciatic nerve was cut were prepared. After 21 days, the temperature changes and the muscle weights in the lower limbs were measured. To assess nerve damage, the L1–6 sympathetic ganglia were immunostained with activating transcription factor 3 (ATF3) antibody.
Results
In the Low-dose, High-dose, and FAC groups, a decrease in temperature was predominantly observed in the left limb. In the High-dose and SNC groups, the weight of the soleus muscle and extensor digitorum longus in the left limb decreased; however, no weight changes were observed in the Low-dose and FAC groups. Conversely, the weight of the gastrocnemius muscle significantly decreased in the Low-dose, High-dose, FAC, and SNC groups. In the High-dose and SNC groups, the number of ATF3-positive cells in the sympathetic ganglia significantly increased, and in the Low-dose, a small number of ATF3-positive cells were observed. However, ATF3-positive cells were rarely observed in the FAC and NS groups.
Conclusion
We established an ALI rat model using microsized gelatin beads. The results of this study suggest that autonomic neuropathy in ALI is related to both muscle damage and peripheral neuropathy.
In 2010, WHO published a “Framework for action on interprofessional education and collaborative practice.” Interprofessional education (IPE) is now being conducted in various ways. We have been ...holding cadaver dissection seminars to provide opportunities for medical students, nursing students, and nurse practitioner (NP) students to learn together. In this study, we investigated the effect of learning about IPE in cadaver dissection seminars. The seminars were held for 5 days each in 2021 and 2022 (the number of days of participation was arbitrary). In the seminars, teams of 3–5 participants with the same theme collaborated to dissect a single donated cadaver. Teams were made up of participants with different departments: 29 medical students, 12 NP students, and 20 nursing students participated in the seminar, and participants were surveyed before and after the seminars. The Readiness for Interprofessional Learning Scale (RIPLS) scores before and after the dissection seminar increased significantly overall. The scores of medical and nursing students increased significantly, but those of NP students did not significantly change. In terms of the number of days of participation, a significant increase in scores was found for participants who participated for ≥ 2 days. Overall, a significant positive correlation was found between intrinsic motivation to learn and RIPLS scores. For medical students, a significant negative correlation was noted between extrinsic motivation and RIPLS scores. Cadaver dissection seminars conducted by medical, nursing, and NP students demonstrated IPE learning effect on medical students and undergraduate nursing students.
The recurrent peroneal nerve (RPN) branches from the common peroneal nerve or the deep peroneal nerve and it innervates to the lower patellar region. It has recently been reported that damage to the ...RPN causes pain in the lower patellar region; therefore, this study examined the recurrent position and the innervation pattern of the RPN.
Cases of knee deformity or atrophy were excluded, and 50 legs (25 males and 25 females) of 34 cadavers (15 males and 19 females) were examined to assess the recurrent position and the innervation pattern of the RPN.
The recurrent position of the RPN was 27.9 ± 3.6 mm from the tip of the fibula. The RPN innervated to the patellar tendon in five of the 50 legs (10%), to the infrapatellar fat pad in 13 legs (26%), and to both the patellar tendon and the infrapatellar fat pad in 20 legs (40%), and to neither the patellar tendon nor the infrapatellar fat pad in 12 legs (24%). No significant sex differences were observed in the recurrent position and the innervation pattern of the RPN.
In all cases, the recurrent position of the RPN was almost fixed from the tip of the fibula. The RPN frequently innervated to the patellar tendon or the infrapatellar fat pad (76%) in both males and females. These findings would be useful in knee surgery to preserve the RPN or for the diagnosis of pain in the lower patellar region.
Arteries receive vascular branches (VBs) from peripheral nerves. VBs are thought to be involved in arterial constriction. Although the anterior tibial artery (ATA) receives VBs, information on their ...branching patterns and distribution areas remains limited. The aim of this study was to investigate the anatomical structures of the VBs reaching the ATA. Forty cadaver limbs were examined to assess the branching patterns and distribution areas of the VBs reaching the ATA. The VBs reaching the ATA ramified from the deep fibular nerve (DFN), and the ATA received two or three VBs in each limb. The following mean distances from the head of fibula to the points at which the VBs reached the ATA were measured: all the VBs, 1st VB, 2nd VB and 3rd VB. The measurements were 51.5 ± 23.2 mm, 33.3 ± 3.7 mm, 53.3 ± 18.6 mm, and 72.2 ± 24.5 mm, respectively. In all limbs, the DFN and the ATA converged after the DFN branched into the 1st VB. The 2nd VB in 38 of 40 limbs and the 3rd VB in 20 of 32 limbs were distributed in the ATA proximal to the convergence point of the ATA and the DFN. These findings revealed that all VBs reaching the ATA ramified from the DFN in all limbs. The ATA received two or three VBs, and all the 1st VBs distributed to the ATA proximal to the convergence point.
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