Pub Date : 2024-08-22DOI: 10.3390/pharmaceutics16081104
Jian Zhang, Jicheng Shu, Rhett W Stout, Paul S Russo, Zhijun Liu
Paclitaxel, which features low water solubility and permeability, is an efflux pump substrate. The current paclitaxel drugs are given intravenously after resolving the solubility issue. Yet, oral delivery to achieve therapeutic bioavailability is not effective due to low absorption. This study evaluated a natural compound, rubusoside, to improve oral bioavailability in an animal model. Free paclitaxel molecules were processed into nano-micelles formed in water with rubusoside. The particle size of the nano-micelles in water was determined using dynamic light scattering. The oral bioavailability of paclitaxel in nano-micelles was determined against Cremophor/alcohol-solubilized Taxol after oral and intravenous administration to pre-cannulated Sprague Dawley rats. When loaded into the rubusoside-formed nano-micelles, paclitaxel reached a supersaturated concentration of 6 mg/mL, 60,000-fold over its intrinsic saturation of 0.1 µg/mL. The mean particle size was 4.7 ± 0.7 nm in diameter. Compared with Taxol®, maximum blood concentration was increased by 1.5-fold; the time to reach maximum concentration shortened to 0.8 h from 1.7 h; and, relative oral bioavailability increased by 88%. Absolute oral bioavailability was 1.7% and 1.3% for the paclitaxel nano-micelles and Taxol®, respectively. Solubilizing paclitaxel with rubusoside was successful, but oral bioavailability remained low. Further inhibition of the efflux pump and/or first metabolism may allow more oral paclitaxel to enter systemic circulation.
{"title":"Solubilization of Paclitaxel with Natural Compound Rubusoside toward Improving Oral Bioavailability in a Rodent Model.","authors":"Jian Zhang, Jicheng Shu, Rhett W Stout, Paul S Russo, Zhijun Liu","doi":"10.3390/pharmaceutics16081104","DOIUrl":"10.3390/pharmaceutics16081104","url":null,"abstract":"<p><p>Paclitaxel, which features low water solubility and permeability, is an efflux pump substrate. The current paclitaxel drugs are given intravenously after resolving the solubility issue. Yet, oral delivery to achieve therapeutic bioavailability is not effective due to low absorption. This study evaluated a natural compound, rubusoside, to improve oral bioavailability in an animal model. Free paclitaxel molecules were processed into nano-micelles formed in water with rubusoside. The particle size of the nano-micelles in water was determined using dynamic light scattering. The oral bioavailability of paclitaxel in nano-micelles was determined against Cremophor/alcohol-solubilized Taxol after oral and intravenous administration to pre-cannulated Sprague Dawley rats. When loaded into the rubusoside-formed nano-micelles, paclitaxel reached a supersaturated concentration of 6 mg/mL, 60,000-fold over its intrinsic saturation of 0.1 µg/mL. The mean particle size was 4.7 ± 0.7 nm in diameter. Compared with Taxol<sup>®</sup>, maximum blood concentration was increased by 1.5-fold; the time to reach maximum concentration shortened to 0.8 h from 1.7 h; and, relative oral bioavailability increased by 88%. Absolute oral bioavailability was 1.7% and 1.3% for the paclitaxel nano-micelles and Taxol<sup>®</sup>, respectively. Solubilizing paclitaxel with rubusoside was successful, but oral bioavailability remained low. Further inhibition of the efflux pump and/or first metabolism may allow more oral paclitaxel to enter systemic circulation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the ever-changing landscape of modern medicine, we face an important moment where the interplay of disease, drugs, and patients defines a new paradigm [...].
{"title":"Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine.","authors":"Cristina Manuela Drăgoi, Alina Crenguța Nicolae, Ion-Bogdan Dumitrescu","doi":"10.3390/pharmaceutics16081107","DOIUrl":"10.3390/pharmaceutics16081107","url":null,"abstract":"<p><p>In the ever-changing landscape of modern medicine, we face an important moment where the interplay of disease, drugs, and patients defines a new paradigm [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/pharmaceutics16081106
Krzysztof Kaczmarek, Jolanta Artym, Joanna Bojarska, Barbara Pacholczyk-Sienicka, Joanna Waśko, Ingrid Jelemenska, Wojciech M Wolf, Martin Breza, Michał Zimecki
The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-β3-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01-P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-β3-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-β3-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.
{"title":"The Immunosuppressive Properties of Cyclo-[<i>D</i>-Pro-Pro-<i>β</i><sup>3</sup>-HoPhe-Phe-] Tetrapeptide Selected from Stereochemical Variants of Cyclo-[Pro-Pro-<i>β</i><sup>3</sup>-HoPhe-Phe-] Peptide.","authors":"Krzysztof Kaczmarek, Jolanta Artym, Joanna Bojarska, Barbara Pacholczyk-Sienicka, Joanna Waśko, Ingrid Jelemenska, Wojciech M Wolf, Martin Breza, Michał Zimecki","doi":"10.3390/pharmaceutics16081106","DOIUrl":"10.3390/pharmaceutics16081106","url":null,"abstract":"<p><p>The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-<i>β</i><sup>3</sup>-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of <i>L</i>-amino acids by <i>D</i>-amino acids (a series of peptides denoted as P01-P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[<i>D</i>-Pro-Pro-<i>β</i><sup>3</sup>-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-<i>D</i>-<i>β</i><sup>3</sup>-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/pharmaceutics16081103
Christoph Rosenbaum, Naemi Gerds, Liliane Hack, Werner Weitschies
Fiber-based technologies are widely used in various industries, but their use in pharmaceuticals remains limited. While melt extrusion is a standard method for producing medical fibers such as sutures, it is rarely used for pharmaceutical fiber-based dosage forms. The EsoCap system is a notable exception, using a melt-extruded water-soluble filament as the drug release trigger mechanism. The challenge of producing drug-loaded fibers, particularly due to the use of spinning oils, and the processing of the fibers are addressed in this work using other approaches. The aim of this study was to develop processes for the production and processing of pharmaceutical fibers for targeted drug delivery. Fibers loaded with polyvinyl alcohol and fluorescein sodium as a model drug were successfully prepared by a continuous melt extrusion process and directly spun. These fibers exhibited uniform surface smoothness and consistent tensile strength. In addition, the fibers were further processed into tubular dosage forms using a modified knitting machine and demonstrated rapid drug release in a flow cell.
{"title":"Scalability of API-Loaded Multifilament Yarn Production by Hot-Melt Extrusion and Evaluation of Fiber-Based Dosage Forms.","authors":"Christoph Rosenbaum, Naemi Gerds, Liliane Hack, Werner Weitschies","doi":"10.3390/pharmaceutics16081103","DOIUrl":"10.3390/pharmaceutics16081103","url":null,"abstract":"<p><p>Fiber-based technologies are widely used in various industries, but their use in pharmaceuticals remains limited. While melt extrusion is a standard method for producing medical fibers such as sutures, it is rarely used for pharmaceutical fiber-based dosage forms. The EsoCap system is a notable exception, using a melt-extruded water-soluble filament as the drug release trigger mechanism. The challenge of producing drug-loaded fibers, particularly due to the use of spinning oils, and the processing of the fibers are addressed in this work using other approaches. The aim of this study was to develop processes for the production and processing of pharmaceutical fibers for targeted drug delivery. Fibers loaded with polyvinyl alcohol and fluorescein sodium as a model drug were successfully prepared by a continuous melt extrusion process and directly spun. These fibers exhibited uniform surface smoothness and consistent tensile strength. In addition, the fibers were further processed into tubular dosage forms using a modified knitting machine and demonstrated rapid drug release in a flow cell.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/pharmaceutics16081102
Charitini Volitaki, Andrew Lewis, Duncan Q M Craig, Asma Buanz
Mesoporous silica particles (MSPs) have been investigated as potential carriers to increase the apparent solubility and dissolution rate of poorly water-soluble drugs by physically stabilising the amorphous nature of the loaded drug. In preparing such systems, it is recognized that the loading method has a critical impact on the physical state and performance of the drug. To date, there has been very limited investigation into the use of electrospraying for loading drugs into mesoporous silica. In this study, we further explore the use of this approach, in particular as a means of producing amorphous and high drug-loaded MSPs; the study includes an investigation of the effect of drug loading and MSP concentration on the formulation performance and process. A comparison with rotary evaporation, a more widely utilised loading technique, was conducted to assess the relative effectiveness of electrospraying. The physical state of the drug in the formulations was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The drug release profiles were determined by a comparative in vitro drug release test. Electrospraying successfully produced formulations containing amorphous drug even at a high drug loading. In contrast, while itraconazole was present in amorphous form at the lower drug-loaded formulations produced by rotary evaporation, the drug was in the crystalline state at the higher loadings. The percentage of drug released was enhanced up to ten times compared to that of pure itraconazole for all the formulations apart from the highest loaded (crystalline) formulation prepared by rotary evaporation. Supersaturation for at least six hours was maintained by the formulations loaded with up to 30 mg/mL itraconazole produced by electrospraying. Overall, the results of this study demonstrate that electrospraying is capable of producing amorphous drug-loaded MSPs at high loadings, with associated favourable release characteristics. A comparison with the standard rotary evaporation approach indicates that electrospraying may be more effective for the production of higher loadings of amorphous material.
介孔二氧化硅颗粒(MSPs)是一种潜在的载体,可通过物理方式稳定所负载药物的无定形性质,从而提高水溶性差药物的表观溶解度和溶解速率。在制备此类系统时,人们认识到装载方法对药物的物理状态和性能有着至关重要的影响。迄今为止,利用电喷雾将药物装入介孔二氧化硅的研究非常有限。在本研究中,我们进一步探讨了这种方法的使用,特别是作为生产无定形和高药物负载介孔二氧化硅的一种手段;研究包括调查药物负载和介孔二氧化硅浓度对制剂性能和工艺的影响。为了评估电喷雾技术的相对有效性,研究人员将其与旋转蒸发技术(一种更广泛使用的负载技术)进行了比较。使用粉末 X 射线衍射(PXRD)和差示扫描量热法(DSC)评估了制剂中药物的物理状态。药物释放曲线是通过体外药物释放对比试验确定的。即使药物含量较高,电喷雾法也能成功制备出含有无定形药物的制剂。相反,在旋转蒸发法制备的低药物载量制剂中,伊曲康唑呈无定形状态,而在高载量制剂中,药物呈结晶状态。与纯净的伊曲康唑相比,除了旋转蒸发法制备的最高载药量(结晶)制剂外,其他所有制剂的药物释放率都提高了 10 倍。电喷雾法制备的伊曲康唑载量高达 30 毫克/毫升的制剂至少能保持六小时的过饱和状态。总之,这项研究的结果表明,电喷雾法能够制备出高负荷的无定形药物负载 MSP,并具有相关的良好释放特性。与标准旋转蒸发法的比较表明,电喷雾法对于生产较高负载量的无定形材料可能更为有效。
{"title":"Electrospraying as a Means of Loading Itraconazole into Mesoporous Silica for Enhanced Dissolution.","authors":"Charitini Volitaki, Andrew Lewis, Duncan Q M Craig, Asma Buanz","doi":"10.3390/pharmaceutics16081102","DOIUrl":"10.3390/pharmaceutics16081102","url":null,"abstract":"<p><p>Mesoporous silica particles (MSPs) have been investigated as potential carriers to increase the apparent solubility and dissolution rate of poorly water-soluble drugs by physically stabilising the amorphous nature of the loaded drug. In preparing such systems, it is recognized that the loading method has a critical impact on the physical state and performance of the drug. To date, there has been very limited investigation into the use of electrospraying for loading drugs into mesoporous silica. In this study, we further explore the use of this approach, in particular as a means of producing amorphous and high drug-loaded MSPs; the study includes an investigation of the effect of drug loading and MSP concentration on the formulation performance and process. A comparison with rotary evaporation, a more widely utilised loading technique, was conducted to assess the relative effectiveness of electrospraying. The physical state of the drug in the formulations was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The drug release profiles were determined by a comparative in vitro drug release test. Electrospraying successfully produced formulations containing amorphous drug even at a high drug loading. In contrast, while itraconazole was present in amorphous form at the lower drug-loaded formulations produced by rotary evaporation, the drug was in the crystalline state at the higher loadings. The percentage of drug released was enhanced up to ten times compared to that of pure itraconazole for all the formulations apart from the highest loaded (crystalline) formulation prepared by rotary evaporation. Supersaturation for at least six hours was maintained by the formulations loaded with up to 30 mg/mL itraconazole produced by electrospraying. Overall, the results of this study demonstrate that electrospraying is capable of producing amorphous drug-loaded MSPs at high loadings, with associated favourable release characteristics. A comparison with the standard rotary evaporation approach indicates that electrospraying may be more effective for the production of higher loadings of amorphous material.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/pharmaceutics16081105
Felipe S Arruda, Fernanda D Tomé, Anália C Milhomem, Pablo I R Franco, Allisson B Justino, Rodrigo R Franco, Erica C Campos, Foued S Espindola, Danilo F Soave, Mara Rubia N Celes
Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.
{"title":"Curcumin Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Increases Survival in Mice.","authors":"Felipe S Arruda, Fernanda D Tomé, Anália C Milhomem, Pablo I R Franco, Allisson B Justino, Rodrigo R Franco, Erica C Campos, Foued S Espindola, Danilo F Soave, Mara Rubia N Celes","doi":"10.3390/pharmaceutics16081105","DOIUrl":"10.3390/pharmaceutics16081105","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy.
{"title":"Drug-Loaded Bioscaffolds for Osteochondral Regeneration.","authors":"Yifan Tong, Jiaqi Yuan, Zhenguang Li, Cuijun Deng, Yu Cheng","doi":"10.3390/pharmaceutics16081095","DOIUrl":"10.3390/pharmaceutics16081095","url":null,"abstract":"<p><p>Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.3390/pharmaceutics16081097
Camila Beatriz Barros Araújo, José de Oliveira Alves Júnior, Mariana Rillo Sato, Kammila Martins Nicolau Costa, Jéssica Roberta Lima, Bolívar Ponciano Goulart de Lima Damasceno, Francisco José Batista de Lima Junior, Bruna Galdorfini Chiari Andréo, Vanda Lucia Dos Santos, João Augusto Oshiro-Junior
This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with Annona muricata concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.
{"title":"The Development and Pre-Clinical Anti-Inflammatory Efficacy of a New Transdermal Ureasil-Polyether Hybrid Matrix Loaded with Flavonoid-Rich <i>Annona muricata</i> Leaf Extract.","authors":"Camila Beatriz Barros Araújo, José de Oliveira Alves Júnior, Mariana Rillo Sato, Kammila Martins Nicolau Costa, Jéssica Roberta Lima, Bolívar Ponciano Goulart de Lima Damasceno, Francisco José Batista de Lima Junior, Bruna Galdorfini Chiari Andréo, Vanda Lucia Dos Santos, João Augusto Oshiro-Junior","doi":"10.3390/pharmaceutics16081097","DOIUrl":"10.3390/pharmaceutics16081097","url":null,"abstract":"<p><p>This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with <i>Annona muricata</i> concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.3390/pharmaceutics16081099
Okhee Yoo, Edith Tang, Md Lokman Hossain, Britta S von Ungern-Sternberg, David Sommerfield, Chloe Heath, Neil Hauser, R Nazim Khan, Cornelia Locher, Minh Nguyen, Lee Yong Lim
Oral liquid prednisolone medications have poor acceptance among paediatric patients due to ineffective masking of the bitterness taste of prednisolone. This study aimed to develop a child-friendly prednisolone tablet using a patented chewable chocolate-based delivery system (CDS) previously applied successfully to mask the bitterness tastes of midazolam and tramadol. Prednisolone sodium phosphate (PSP) and prednisolone base (PB) CDS tablets were prepared, and the manufacturing process was optimised using a design of experiments (DoE) approach. Stability was assessed by quantifying residual drug content via a validated HPLC assay. A pilot randomised crossover taste study involving 25 young adult volunteers evaluated taste-masking effectiveness against Redipred™, a commercial oral PSP liquid medicine. The results showed that the PSP CDS tablet was chemically stable following storage for three months at ambient temperature, while the PB CDS tablet was unstable. The optimised PSP CDS tablet, manufactured at 50 °C with a stirring time of 26 h, was found to release over 80% of its drug load within 20 min in 0.1 M HCl and had a significantly better mean taste score compared to Redipred™ (7.08 ± 2.40 vs. 5.60 ± 2.33, p = 0.03). Fifty six percent of the participants preferred the PSP CDS tablet. In conclusion, compared to Redipred™, the CDS technology provided a more effective taste masking of PSP, potentially offering a child-friendly prednisolone formulation with improved compliance, dosing accuracy, and storage stability.
{"title":"The Development of a Chocolate-Based Chewable Tablet of Prednisolone-Enhancing the Palatability of Steroids for Pediatric Use.","authors":"Okhee Yoo, Edith Tang, Md Lokman Hossain, Britta S von Ungern-Sternberg, David Sommerfield, Chloe Heath, Neil Hauser, R Nazim Khan, Cornelia Locher, Minh Nguyen, Lee Yong Lim","doi":"10.3390/pharmaceutics16081099","DOIUrl":"10.3390/pharmaceutics16081099","url":null,"abstract":"<p><p>Oral liquid prednisolone medications have poor acceptance among paediatric patients due to ineffective masking of the bitterness taste of prednisolone. This study aimed to develop a child-friendly prednisolone tablet using a patented chewable chocolate-based delivery system (CDS) previously applied successfully to mask the bitterness tastes of midazolam and tramadol. Prednisolone sodium phosphate (PSP) and prednisolone base (PB) CDS tablets were prepared, and the manufacturing process was optimised using a design of experiments (DoE) approach. Stability was assessed by quantifying residual drug content via a validated HPLC assay. A pilot randomised crossover taste study involving 25 young adult volunteers evaluated taste-masking effectiveness against Redipred™, a commercial oral PSP liquid medicine. The results showed that the PSP CDS tablet was chemically stable following storage for three months at ambient temperature, while the PB CDS tablet was unstable. The optimised PSP CDS tablet, manufactured at 50 °C with a stirring time of 26 h, was found to release over 80% of its drug load within 20 min in 0.1 M HCl and had a significantly better mean taste score compared to Redipred™ (7.08 ± 2.40 vs. 5.60 ± 2.33, <i>p</i> = 0.03). Fifty six percent of the participants preferred the PSP CDS tablet. In conclusion, compared to Redipred™, the CDS technology provided a more effective taste masking of PSP, potentially offering a child-friendly prednisolone formulation with improved compliance, dosing accuracy, and storage stability.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.3390/pharmaceutics16081098
Weining Yin, Junting Yao, Xuwei Leng, Chengbang Ma, Xiaoling Chen, Yangyang Jiang, Tao Wang, Tianbao Chen, Chris Shaw, Mei Zhou, Lei Wang
Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from Phyllomedusidae frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH2), identified from the skin secretion of Phyllomedusa tomopterna, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.
{"title":"Enhancement of Antimicrobial Function by L/D-Lysine Substitution on a Novel Broad-Spectrum Antimicrobial Peptide, Phylloseptin-TO2: A Structure-Related Activity Research Study.","authors":"Weining Yin, Junting Yao, Xuwei Leng, Chengbang Ma, Xiaoling Chen, Yangyang Jiang, Tao Wang, Tianbao Chen, Chris Shaw, Mei Zhou, Lei Wang","doi":"10.3390/pharmaceutics16081098","DOIUrl":"10.3390/pharmaceutics16081098","url":null,"abstract":"<p><p>Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from <i>Phyllomedusidae</i> frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH<sub>2</sub>), identified from the skin secretion of <i>Phyllomedusa tomopterna</i>, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against <i>Staphylococcus aureus</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}