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A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties. Spray freeze-drying (SFD) is a method to produce inhalable powder formulation. In this study, we prepared inhalable powder formulations of mRNA-LNPs without deliquescence excipients using pH-modified SFD, which strengthens the interaction between mRNA and ionizable lipids of LNPs by acidic pH modifier, leading to retention of the encapsulated structure of mRNA-LNPs even after SFD. Powdered mRNA-LNPs were suitable for inhalation, and mRNA was encapsulated in LNPs after SFD. The mRNA encapsulation efficiency and mRNA transfection efficiency of pH-modified SFD-mediated powdered mRNA-LNPs were higher than those of conventional SFD, although they were significantly lower than those of liquid intact mRNA-LNPs. However, after long-term storage, the powdered formulation of the mRNA-LNPs exhibited higher mRNA transfection efficiency than liquid mRNA-LNP. Powdered mRNA-LNPs also exerted their function in air-liquid interface cultivation and in vivo intratracheal administration. Collectively, the powder formulation of mRNA-LNPs especially prepared by SFD is expected to be applied for dry powder inhalers.
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Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm. The HGNPs were hollow and the surface had protruding structures when prepared using high concentrations of HAuCl4. The simultaneous nucleation of a sacrificial AgCl template and Au nanoparticles may affect the resulting HGNPs. Diethyldithiocarbamate (DDTC) is metabolized from disulfiram and is a repurposed drug currently attracting attention. The chelation of DDTC with copper ion (DDTC-Cu) has been investigated for treating glioma, and here we confirmed the cytotoxic effect of DDTC-Cu towards rat C6 glioma cells in vitro. HGNPs alone were biocompatible and showed little cytotoxicity, whereas a mixture of DDTC-Cu and HGNPs was cytotoxic in a dose dependent manner. The temperature of HGNPs was increased by NIR-laser irradiation. The photothermal effect on HGNPs under NIR-laser irradiation resulted in cytotoxicity towards C6 cells and was dependent on the irradiation time. Photothermal therapy by HGNPs combined and DDTC-Cu was highly effective, suggesting that this combination approach hold promise as a future glioma therapy.
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Antineoplásicos , Glioma , Nanopartículas Metálicas , Animais , Ratos , Ditiocarb/farmacologia , Cobre , Ouro , Terapia Fototérmica , Antineoplásicos/farmacologia , Linhagem Celular , Glioma/tratamento farmacológicoRESUMO
Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential. The method of incorporating SG into the lipid or aqueous phase of the liposome did not notably impact the characteristics of the liposomes but the hydration media had a substantial effect on the entrapment efficiency of 5-ASA. In vitro drug release in different fluids simulating distinct gastrointestinal tract sections, indicated pH-dependent disintegration of the coating layer of coated SG-containing liposomes. The majority of the drug was retained when subjected to simulated gastric fluid (SGF) and fed-state simulated intestinal fluid (FeSSIF) (≈ 37% release after 2 h in SGF pH 1.2, followed by 3 h in FeSSIF pH 5). The remaining drug was subsequently released in phosphate-buffered saline pH 7.4 (≈ 85% release within 24 h). Increasing SG concentration in the liposomes decreased the amount of drug released in FeSSIF. Similar results were observed when SG was replaced with sodium taurocholate. Cellular uptake studies in Caco-2 cells demonstrated that all liposomal formulations (conventional liposomes, bile salt-containing liposomes, and coated bile salt-containing liposomes) have shown to be equally effective at increasing the cellular uptake compared to free fluorescein solution. In the pharmacokinetic study, coated bile salt-containing liposomes showed a lower Cmax and prolonged residence in the gastrointestinal tract in comparison to conventional liposomes. Taken together, these findings suggest that the polymer-coated bile salt-containing liposomes have the potential to serve as a drug delivery system targeted at the colon.
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Lipossomos , Mesalamina , Humanos , Animais , Lipossomos/química , Mesalamina/metabolismo , Ácidos e Sais Biliares , Células CACO-2 , Ácido Glicocólico/química , Colo/metabolismoRESUMO
Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated. The azithromycin-loaded contact lenses were composed of the cross-linking reagent polyethylene glycol diacrylate (PEGDA), PEG 400 as a solvent, a photoinitiator, and azithromycin. The 3D-printed contact lenses were fabricated successfully, and formulations with lower PEGDA concentrations produced thicker lenses. The mechanical strength of the PEGDA-based contact lenses was dependent on the amount of PEGDA and was improved by a second curing process. Drug release from 3D-printed contact lenses was reduced in the samples with a second curing process. The azithromycin-loaded contact lenses exhibited antimicrobial effects in vitro for both Gram-positive and -negative bacteria. These results suggest that 3D-printed contact lenses containing antibiotics are an effective model for treating eye infections by controlling drug release.
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Azitromicina , Lentes de Contato , Tecnologia Farmacêutica/métodos , Preparações de Ação Retardada , Polietilenoglicóis , Liberação Controlada de Fármacos , Impressão TridimensionalRESUMO
Poly lactic-co-glycolic acid (PLGA) microparticles have been formulated to allow the sustained release of numerous drugs, including antibodies. It is well-known that antibodies are susceptible to chemical and physical stress; therefore, it is necessary to be loaded on PLGA microparticles under mild conditions. In the present study, we constructed cationic porous PLGA microparticles that could be electrostatically adsorbed with infliximab as a model antibody. Cationic porous PLGA microparticles were prepared using the double emulsion method by adding polyethyleneimine and ammonium bicarbonate. After antibody loading, surface pores closure was achieved by mild heating. The size of the optimized formulation was approximately 5 µm, exhibiting a positive charge. The loaded antibody was gradually released from the formulation over 56 days. Based on a tumor necrosis factor (TNF)-α inhibition assay, the released infliximab maintained its pharmacological activity. Collectively, we successfully loaded antibodies into PLGA microparticles while maintaining activity and demonstrating long-acting properties.
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Anticorpos , Glicóis , Infliximab , Porosidade , BioensaioRESUMO
Lung cancer is the leading cause of cancer-related death. In addition to new innovative approaches, practical strategies that improve the efficacy of already available drugs are urgently needed. In this study, an inhalable dry powder formulation is used to repurpose flubendazole, a poorly soluble anthelmintic drug with potential against a variety of cancer lineages. Flubendazole nanocrystals were obtained through nanoprecipitation, and dry powder was produced by spray drying. Through fractional factorial design, the spray drying parameters were optimized and the impact of formulation on aerolization properties was clarified. The loading limitations were clarified through response surface methodology, and a 15% flubendazole loading was feasible through the addition of 20% L-leucine, leading to a flubendazole particle size of 388.6 nm, median mass aerodynamic diameter of 2.9 µm, 50.3% FPF, emitted dose of 83.2% and triple the initial solubility. Although the cytotoxicity of this formulation in A549 cells was limited, the formulation showed a synergistic effect when associated with paclitaxel, leading to a surprising 1000-fold reduction in the IC50. Compared to 3 cycles of paclitaxel alone, a 3-cycle model combined treatment increased the threshold of cytotoxicity by 25% for the same dose. Our study suggests, for the first time, that orally inhaled flubendazole nanocrystals show high potential as adjuvants to increase cytotoxic agents' potency and reduce adverse effects.
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Adjuvantes Imunológicos , Nanopartículas , Pós , Adjuvantes Farmacêuticos , Paclitaxel/farmacologiaRESUMO
Intranasal administration has attracted increasing attention as a drug delivery approach based on nose-to-brain drug delivery from the nasal cavity to brain tissue directly, bypassing the blood-brain barrier. However, application of the method to poorly water-soluble drugs is potentially limited due to low aqueous solubility and dissolution, which can hinder drug transfer to brain tissue. In the present study, we focused on an amorphous solid dispersion (ASD) technique to improve drug dissolution. A carbamazepine-loaded ASD model drug was prepared using the solvent evaporation method (ASD-1). After screening six water-soluble polymer carriers, polyvinyl alcohol (PVA)-based ASD-1 formulation exhibited the most rapid and highest drug dissolution under experimental conditions in the nasal cavity (pH 6.0). A carbamazepine suspension dispersed with a PVA-ASD-1 formulation exhibited enhanced drug delivery into plasma and brain tissue of rats in vivo. A spray-dried powder formulation of PVA-ASD (PVA-ASD-2) exhibited improved drug dissolution and in vivo drug transfer. Our key finding is that the spray-dried PVA-ASD-2 formulation exhibited higher brain/plasma ratios than the PVA-ASD-1 suspension formulation. Our physical characterization data and demonstration of improved drug transfer suggest that ASD-based intranasal formulations hold promise for drug delivery to the brain.
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Química Farmacêutica , Água , Ratos , Animais , Química Farmacêutica/métodos , Preparações Farmacêuticas , Pós , Cristalização , Solubilidade , Liberação Controlada de Fármacos , Água/química , Encéfalo , Composição de Medicamentos/métodosRESUMO
Hospital-acquired pneumonia is an important infectious disease that requires special management and therapy for patients with compromised immunity, as opportunistic infections with microorganisms such as Pseudomonas aeruginosa can be fatal. Nanoparticle-based drug delivery to lung tissue provides several advantages in the treatment of respiratory diseases. In the current study, inhalable nanocomposite particles consisting of microparticles containing solid-state arbekacin (ABK) nanoparticles coated with hydrophobic surfactant (ABK-SD nanoparticles) were prepared using a spray dryer equipped with a two-solution mixing-type spray nozzle we previously developed. ABK-SD/mannitol (MAN) nanocomposite particles were obtained from ABK-SD nanoparticles by varying the amounts of hydrophobic surfactant and ABK. The aerosol performance of ABK-SD/MAN nanocomposite particles was superior to that of ABK-MAN microparticles in terms of the fine particle fraction (28.4 ± 5.4%, ABK-SD/MAN nanocomposite particles; 11.4 ± 7.6%, ABK-MAN microparticles). These results suggest that ABK-SD/MAN nanocomposite particles are suitable for use in inhalation drug formulations and useful for the treatment of lung infections involving Pseudomonas aeruginosa.
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Nanocompostos , Nanopartículas , Humanos , Pseudomonas aeruginosa , Composição de Medicamentos/métodos , Administração por Inalação , Nanocompostos/química , Nanopartículas/química , Tensoativos , Manitol , Tamanho da PartículaRESUMO
Wear-resistant polymers and ceramics-based media have been used to pulverize the bulk powder of poorly water-soluble drugs to nanoscale size in conventional milling; however, contamination of such media is still an issue in the context of drug formulation manufacturing. In the present study, we developed a novel method for pulverizing the particles of a poorly water-soluble drug, ketoprofen, to nanoscale size by mixing mannitol and polypropylene glycol as a safe pulverizing medium. The ketoprofen nanoparticles were prepared using a Hoover automatic muller, equipment that traditionally has been used for the mixing of paint and ink. This process represents a novel application of this machine for the on-demand preparation of nanoparticulate formulations for use in the clinical setting. The optimal composition of the drug formulation was determined by designing an experiment consisting of the central composite design and responsive surface method. We obtained a design space that yielded ketoprofen nanoparticles with targeted particle size, poly-dispersity index, and drug release properties. We validated the manufacturing conditions by preparing ketoprofen nanoparticles in four compositions. Thus, the present study provided useful information regarding not only simple and effective contamination-free milling but also the experimental conditions need to produce nanoparticles of a poorly water-soluble drug.
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Cetoprofeno , Nanopartículas , Manitol , Tamanho da Partícula , Composição de Medicamentos/métodos , Água , SolubilidadeRESUMO
Oral mucositis in the oral cavity, caused by radiation therapy and chemotherapy, requires personalized care and therapy due to variations in the lesions of patients. In the present study, we fabricated a model of personalized oral film containing an ibuprofen/lidocaine ionic liquid (IL) for patients with oral mucositis using a pressure-assisted microsyringe-type 3D printer at room temperature. The film contained a Eudragit polymer (L100, EPO, or RSPO) to make the film solid, and the printer ink was composed of organo ink (organic solvent to dissolve both drugs and the Eudragit polymer). The viscosity of the printer ink was assessed to investigate its extrudability. The contact angle and the surface tension at the interface between each liquid printer ink and a solid polypropylene sheet were measured to determine the retention of the ink in 3D printing. The physical properties of IL-loaded Eudragit-based dry films were examined by X-ray diffraction and differential scanning calorimetry. Dissolution tests indicated that IL-loaded films containing a Eudragit polymer exhibited different drug release rates in phosphate buffer (pH 6.8; Eudragit L100 > IL alone > Eudragit EPO > Eudragit RSPO). These results provide useful information for the specific fabrication of IL-loaded polymer-based films using organo inks and pressure-assisted microsyringe-type 3D printers.
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Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient's quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.
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The aim of this study was to prepare a liposomal formulation of a model drug (budesonide) for colonic delivery by incorporating a bile salt (sodium glycocholate, SGC) into liposomes followed by coating with a pH-responsive polymer (Eudragit S100, ES100). The role of the SGC is to protect the liposome from the emulsifying effect of physiological bile salts, while that of ES100 is to protect the liposomes from regions of high acidity and enzymatic activity in the stomach and small intestine. Vesicles containing SGC were prepared by two preparation methods (sonication and extrusion), and then coated by ES100 (ES100-SGC-Lip). ES100-SGC-Lip showed a high entrapment efficiency (>90%) and a narrow size distribution (particle size = 275 nm, polydispersity index < 0.130). The characteristics of liposomes were highly influenced by the concentration of incorporated SGC. The lipid/polymer weight ratio, liposome charge, liposome addition, and mixing rate were critical factors for efficient and uniform coating. In vitro drug release studies in various simulated fluids indicate a pH-dependent dissolution of the coating layer, and the disintegration process of ES100-SGC-Lip was evaluated. In conclusion, the bile salt-containing ES100-coated liposomal formulation has potential for effective oral colonic drug delivery.
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Bioequivalence has been assessed using in vitro dissolution testing, such as in vivo predictive dissolution methodology. However, the assessment of bioequivalence should be performed carefully, considering the effect of the in vivo environment and according to the properties of the drug. The gastric emptying process is a key factor for the assessment of biopharmaceutics classification system class II (BCS class IIa) drugs with acidic properties since they cannot dissolve in the acidic stomach, but do dissolve in the small intestine (SI). The disintegration of a tablet in the stomach affects the distribution/dissolution in the SI due to the difference in the gastric emptying step, which in turn is a result of the varying formulation of the drugs. In this study, we used the reported dynamic pH change method and a novel gastric process simulation (GPS) model, which can compare the gastric emptying of particular-sized drug particles. The in vitro results were compared to clinical data using bioequivalent and bioinequivalent products of candesartan cilexetil. It was revealed that the dynamic pH change method was inappropriate, whereas the amount of filtered drug in GPS studies with 20 and 50 µm pore size filters could reflect the clinical results of all products. The evaluation of the gastric emptying process of drug particles less than 50 µm enabled us to assess the bioequivalence because they probably caused the difference in the distribution in the SI. This study demonstrated the utility of the GPS model for the assessment of bioequivalence of BCS class IIa drugs.
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Biofarmácia , Estômago , Biofarmácia/métodos , Simulação por Computador , Solubilidade , Equivalência TerapêuticaRESUMO
3D printing technology is a novel and practical approach for producing unique and complex industrial and medical objects. In the pharmaceutical field, the approval of 3D printed tablets by the US Food and Drug Administration has led to other 3D printed drug formulations and dosage forms being proposed and investigated. Here, we report novel ophthalmologic patches for controlled drug release fabricated using a semi-solid material extrusion-type 3D printer. The patch-shaped objects were 3D printed using hydrogel-based printer inks composed of hypromellose (HPMC), sugar alcohols (mannitol, xylitol), and drugs, then freeze-dried. The viscous properties of the printer inks and patches were dependent on the HPMC and sugar alcohol concentrations. Then, the physical properties, surface structure, water uptake, antimicrobial activity, and drug release profile of lyophilized patches were characterized. Lyophilized ophthalmologic patches with different dosages and patterns were fabricated as models of personalized treatments prepared in hospitals. Then, ophthalmologic patches containing multiple drugs were fabricated using commercially available eye drop formulations. The current study indicates that 3D printing is applicable to producing novel dosage forms because its high flexibility allows the preparation of patient-tailored dosages in a clinical setting.
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Excipientes , Impressão Tridimensional , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Derivados da Hipromelose/química , Comprimidos , Tecnologia FarmacêuticaRESUMO
Confectionery ingredients are expected to enhance the medication adherence of pediatric patients taking bitter-tasting drugs when adequate pediatric medicines are not available in practical settings. Gum is a familiar confectionery, and several drug-loaded gums are on the market as medicated chewing gums. In this study, medical gum tablets composed of confectionery xylitol gum and a drug (ibuprofen or acetaminophen) were prepared and evaluated for the purpose of potential hospital applications. The effect of the sintering process, a heating treatment, on the physical properties of the solid materials was also examined. The sintering process markedly improved the hardness of the gum tablets. The sintering temperature and time affected the hardness of both ibuprofen- and acetaminophen-loaded gum tablets, whereas heat treatment around the melting point of ibuprofen or xylitol and longer heat treatment resulted in failure of the preparation or a reduction in hardness. The sintered gum tablets exhibited a delayed drug release profile in artificial saliva after an in vitro chewing test. The current results provide basic and useful information about the preparation of gum-containing tablets in future clinical settings.
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Goma de Mascar , Excipientes/química , Adesão à Medicação , Xilitol/química , Acetaminofen/química , Acetaminofen/farmacocinética , Química Farmacêutica , Criança , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Humanos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Saliva/química , Comprimidos , PaladarRESUMO
The application of 3D printing technology to pharmaceuticals is expanding, and 3D-printed drug formulations comprising various materials and excipients have been developed using different types of 3D printers. Here, we used a digital light processing-type 3D printer to fabricate poly(ethylene glycol) diacrylate (PEGDA)-based "ghost tablets" that release entrapped drug but do not disintegrate. Three drugs with different aqueous solubilities were incorporated separately into the tablets, and the effects of printer ink composition and printing conditions on tablet formation and drug release were investigated. We also constructed a simple and effective model to predict the drug release profiles of the 3D-printed PEGDA-based tablets based on printer ink compositions and printing conditions. Drug release profiles were constructed by combining data for the amount of drug released at a specified time (15 hr) predicted by a regression algorithm generated by machine learning (multiple linear regression) and the drug release kinetics model generated by a binary classification algorithm (support vector machine). The proposed prediction model is unique and provides information useful for the development of 3D-printed PEGDA-based tablets as future tailored medicines.
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Excipientes , Tecnologia Farmacêutica , Composição de Medicamentos , Liberação Controlada de Fármacos , Impressão Tridimensional , ComprimidosRESUMO
Nanomedicine is a new medical field involving the use of nanoparticles. Early examples of biocompatible nanomedicines include liposomes (Doxil®) and albumin nanoparticles (Abraxane®), and promising new nanomedicines include nanocarriers such as nanomicelles and nanoemulsions. A new trend towards the use of metal-based nanoparticles, including gold nanoparticles, has led to global clinical trials. These particles exhibit novel properties compared to conventional nanomedicines such as liposomes and albumin nanoparticles. These properties hold promise for nanomedicines, and thus the biodistribution and pharmacokinetics of metal-based nanoparticles should be carefully investigated. This had led to an increasing number of clinical trials investigating metal nanoparticles and inorganic nanoparticles. The present review evaluates multi-functional gold nanoparticles described in recent articles and shows that the unique properties of gold nanoparticles are applicable for not only drug delivery, but also for imaging. The combined therapeutic modality between therapeutics and diagnostics is called "theranostics" and is promising for future personalized cancer therapy. This review also introduces recent research from our laboratory involving the use of various kinds of molecules [polyethylene glycol (PEG), drug/cyclodextrin inclusion complexes, biosimilars and small interfering (siRNAs)] loaded onto and/or conjugated with gold nanoparticles.
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Sistemas de Liberação de Medicamentos , Ouro , Nanopartículas Metálicas , Nanomedicina , Nanotecnologia , Neoplasias/tratamento farmacológico , Albuminas , Materiais Biocompatíveis , Diagnóstico por Imagem , Ouro/farmacocinética , Humanos , Lipossomos , Medicina de PrecisãoRESUMO
The 3D printing of drug formulations is a promising method for preparing tailored medicines following the approval of 3D printed tablets by the US FDA in 2015. Appropriate dosage forms for pediatric patients are deficient because drugs have been developed for mainly adult patients. Here, we fabricated gummy drug formulations for pediatric patients using a 3D bioprinter compatible with semi-solid materials such as hydrogels and pastes. The gummy drug formulations were composed of gelatin, HPMC, reduced syrup, water and the antiepileptic drug lamotrigine. The formulations were extruded from the nozzle of the 3D bioprinter under air pressure and laminated from the bottom in a layer-by-layer process. The incorporation of HPMC aided smooth printing at room temperature, and gelatin and HPMC affected the viscosity of the drug formulation and the printability of the formulations. The strength of the gummy formulations was remarkably influenced by the gelatin concentration. Dissolution tests showed 85% drug release within 15 min from most formulations. The results suggest that 3D printing is an effective method for preparing gummy drug formulations with various shapes in different colors, and that the methodology may improve drug adherence of pediatric patients in future clinical settings.
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Gelatina , Hidrogéis , Criança , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Impressão TridimensionalRESUMO
The application of 3D printing technology for generating tablets is attracting the attention of the pharmaceutical industry following approval of a 3D printed tablet (Spritam) by the US Food and Drug Administration. Here we focused on hollow-type suppository formulations typically prepared as suppository shells by pharmacists in hospitals. We used a fused deposition modeling-type 3D printer and polyvinyl alcohol filament as a water soluble material to print suppository shells with various thicknesses and different inner structures by changing the printing conditions for the 3D designed objects. The hardness of the suppository shell was dependent on the thickness and designed inner structure. An active pharmaceutical ingredient ionic liquid, a novel type of liquid drug formulation, was loaded in the suppository shells. The drug dissolution profile of the suppository formulations differed depending on the type of suppository shell. Composite suppository formulations (two drugs in separate compartments in the suppository shell) were prepared as a model tailored medicine for pediatric patients. Our findings suggest that 3D printing technology is applicable to the preparation of hollow-type suppository formulations and may be compatible with on-site hospital production.
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Impressão Tridimensional , Tecnologia Farmacêutica , Criança , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Supositórios , ComprimidosRESUMO
3D printing technology has been applied to various fields and its medical applications are expanding. Here, we fabricated implantable 3D bio-printed hydrogel patches containing a nanomedicine as a future tailored cancer treatment. The patches were prepared using a semi-solid extrusion-type 3D bioprinter, a hydrogel-based printer ink, and UV-LED exposure. We focused on the composition of the printer ink and semi-synthesized fish gelatin methacryloyl (F-GelMA), derived from cold fish gelatin, as the main component. The low viscosity of F-GelMA due to its low melting point was remarkably improved by the addition of carboxymethyl cellulose sodium (CMC), a pharmaceutical excipient. PEGylated liposomal doxorubicin (DOX), as a model nanomedicine, was incorporated into the hydrogel and liposome stability after photo-polymerization was evaluated. The addition of CMC inhibited particle size increase. Three types of 3D-designed patches (cylinder, torus, gridlines) were produced using a 3D bioprinter. Drug release was dependent on the shape of the 3D-printed patches and UV-LED exposure time. The current study provides useful information for the preparation of 3D printed nanomedicine-based objects.