Pub Date : 2024-11-07DOI: 10.1016/j.ijpharm.2024.124918
Xinmin Wang , Lizhen Huang , Qing Du , Jing Li , Qin Zheng , Yingchong Chen , Pengfei Yue
To improve the retention time and skin-whitening efficacy of Atractylodes macrocephale essential oil (AMO), a novel Pickering emulsion based nanogel loaded with AMO (AMO-PEG) was successfully developed. This formulation employed nano-pearl powder (NPP) as the particle stabilizer for the Pickering emulsion and Bletilla striata polysaccharide (BSP) as the gel matrix. The pH, rheological properties, hardness, and elasticity of AMO-PEG were affected by the ratio of AMO-Pickering emulsion (AMO-PE) to BSP gel matrix. The results showed that AMO-PEG exhibited solid-like behavior and was capable of forming nanogels when the ratio of AMO-PE to BSP was 1:1. AMO-PE and AMO-PEG are two different dosage forms in the preparation of AMO. The effects of varying dosage forms on AMO were evaluated by in vitro transdermal release, skin irritation test, and skin-whitening effect. AMO-PEG conforms to the zero-order kinetic equation (R2 = 0.9189). The skin retention rate of AMO-PEG was 1.37 times higher than that of AMO-PE, indicating that AMO-PEG could continuously and slowly exert the whitening effect of the drugs. Compared with AMO-PE, AMO-PEG significantly increased the inhibition of tyrosinase activity and melanogenesis in B16F10 cells. AMO-PEG can promote the inhibition of B16F10 cells and improve the whitening effect of AMO and BSP. In conclusion, the Pickering emulsion based nanogel appears to be a promising strategy for enhancing the skin-whitening efficacy of both AMO and BSP.
{"title":"Pickering emulsions embedded in Bletilla striata polysaccharide based nanogel for enhancing skin-whitening effect of essential oils","authors":"Xinmin Wang , Lizhen Huang , Qing Du , Jing Li , Qin Zheng , Yingchong Chen , Pengfei Yue","doi":"10.1016/j.ijpharm.2024.124918","DOIUrl":"10.1016/j.ijpharm.2024.124918","url":null,"abstract":"<div><div>To improve the retention time and skin-whitening efficacy of <em>Atractylodes macrocephale</em> essential oil (AMO), a novel Pickering emulsion based nanogel loaded with AMO (AMO-PEG) was successfully developed. This formulation employed nano-pearl powder (NPP) as the particle stabilizer for the Pickering emulsion and <em>Bletilla striata</em> polysaccharide (BSP) as the gel matrix. The pH, rheological properties, hardness, and elasticity of AMO-PEG were affected by the ratio of AMO-Pickering emulsion (AMO-PE) to BSP gel matrix. The results showed that AMO-PEG exhibited solid-like behavior and was capable of forming nanogels when the ratio of AMO-PE to BSP was 1:1. AMO-PE and AMO-PEG are two different dosage forms in the preparation of AMO. The effects of varying dosage forms on AMO were evaluated by <em>in vitro</em> transdermal release, skin irritation test, and skin-whitening effect. AMO-PEG conforms to the zero-order kinetic equation (R<sup>2</sup> = 0.9189). The skin retention rate of AMO-PEG was 1.37 times higher than that of AMO-PE, indicating that AMO-PEG could continuously and slowly exert the whitening effect of the drugs. Compared with AMO-PE, AMO-PEG significantly increased the inhibition of tyrosinase activity and melanogenesis in B16F10 cells. AMO-PEG can promote the inhibition of B16F10 cells and improve the whitening effect of AMO and BSP. In conclusion, the Pickering emulsion based nanogel appears to be a promising strategy for enhancing the skin-whitening efficacy of both AMO and BSP.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124918"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.ijpharm.2024.124914
Claudia Moscheni , Patrizia Sartori , Kaiyue Hu , Silvia Zecchini , Luigi Brambilla , Alessandro Arcari , Alessandra Napoli , Emanuele Mocciaro , Marco Uboldi , Lucia Zema , Cristiana Perrotta , Chiara Castiglioni
Thanks to an environmentally friendly physical treatment of high purity graphite, a good control of the structure of graphene nanoparticles (GNPs) has been obtained with the production of stable and reproducible GNPs water dispersions. The preparation protocol entailed ball-milling of synthetic graphite followed by sonication in water and centrifugation/separation procedures. This way, two different GNPs samples with slightly different structural characteristics were harvested: TOP60, showing an average lateral size of the graphene layers <L> = 70 nm and average number of stacked layers <N> = 4, and BOTTOM60, with <L> = 120 nm and <N> = 6. A detailed structural characterization of GNPs was performed as mandatory pre-requisite to build reliable structure/properties correlations, in terms of both biomedical efficacy and toxicity, aiming at a rationale design of tailored materials for applications in biological environments.
To this end, in this study GNPs were thoroughly characterized, focusing on cytotoxicity, cellular uptake, and inflammatory response, by testing their effect in different cell lines. BOTTOM60 GNPs in culture medium and in the presence of cells showed a tendency to form big aggregates, phenomenon that was probably responsible for their cytotoxicity at high concentrations. On the other hand, TOP60 GNPs showed a diverse behavior depending on the cell type under investigation. Indeed, the nanoparticles were internalized by cells specialized in endo/phagocytosis, such as astrocytoma cells, but not by carcinoma cells of epithelial origin. Moreover, TOP60 GNPs caused a reduction of proliferation only at high concentration and did not trigger an inflammatory response in THP-1-derived macrophages.
The evidence here collected paves the way for further investigations towards the development of GNPs-based drug delivery systems.
{"title":"Tailored graphene nanoparticles for biomedical application: preliminary in vitro characterization of the functionality in model cell lines","authors":"Claudia Moscheni , Patrizia Sartori , Kaiyue Hu , Silvia Zecchini , Luigi Brambilla , Alessandro Arcari , Alessandra Napoli , Emanuele Mocciaro , Marco Uboldi , Lucia Zema , Cristiana Perrotta , Chiara Castiglioni","doi":"10.1016/j.ijpharm.2024.124914","DOIUrl":"10.1016/j.ijpharm.2024.124914","url":null,"abstract":"<div><div>Thanks to an environmentally friendly physical treatment of high purity graphite, a good control of the structure of graphene nanoparticles (GNPs) has been obtained with the production of stable and reproducible GNPs water dispersions. The preparation protocol entailed ball-milling of synthetic graphite followed by sonication in water and centrifugation/separation procedures. This way, two different GNPs samples with slightly different structural characteristics were harvested: TOP60, showing an average lateral size of the graphene layers <L> = 70 nm and average number of stacked layers <N> = 4, and BOTTOM60, with <L> = 120 nm and <N> = 6. A detailed structural characterization of GNPs was performed as mandatory pre-requisite to build reliable structure/properties correlations, in terms of both biomedical efficacy and toxicity, aiming at a rationale design of tailored materials for applications in biological environments.</div><div>To this end, in this study GNPs were thoroughly characterized, focusing on cytotoxicity, cellular uptake, and inflammatory response, by testing their effect in different cell lines. BOTTOM60 GNPs in culture medium and in the presence of cells showed a tendency to form big aggregates, phenomenon that was probably responsible for their cytotoxicity at high concentrations. On the other hand, TOP60 GNPs showed a diverse behavior depending on the cell type under investigation. Indeed, the nanoparticles were internalized by cells specialized in endo/phagocytosis, such as astrocytoma cells, but not by carcinoma cells of epithelial origin. Moreover, TOP60 GNPs caused a reduction of proliferation only at high concentration and did not trigger an inflammatory response in THP-1-derived macrophages.</div><div>The evidence here collected paves the way for further investigations towards the development of GNPs-based drug delivery systems.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124914"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A formerly developed mathematical model describing drug release from hydrophilic matrices (HMs) took into account resistance to drug release given by its dissolution and by the presence of a growing gel layer. Such a model was applied to previously reported release data obtained from HMs made of hydroxypropyl methylcellulose (HPMC), where acetaminophen was used as model drug and a cellulolytic product was added as “active” excipient to attain zero-order release kinetics. The Levich theory applied to acetaminophen intrinsic dissolution rate (IDR) data highlighted the suitability of such a drug for modeling purposes, given its good surface wettability. First assessment of the model ability to describe drug release from the abovementioned systems was carried out on partially coated matrices, representing a simplified physical frame, but results were then confirmed on uncoated systems. Experimental and model release data showed good agreement; therefore, the release-describing equation was combined with that of the global mass balance to obtain two new equations related to erosion and diffusion fronts time evolution. Changes over time in the dissolution and gel contributions to total resistance, calculated using model output parameters, highlighted that the enzyme, through its hydrolytic activity on HPMC, was responsible for a time-dependent reduction of the resistance component related to gel layer.
{"title":"Modeling of drug release, erosion and diffusion fronts movement in high viscosity HPMC matrices containing a cellulolytic enzyme","authors":"Ilaria Filippin , Saliha Moutaharrik , Michela Abrami , Lucia Grassi , Andrea Gazzaniga , Alessandra Maroni , Mario Grassi , Anastasia Foppoli","doi":"10.1016/j.ijpharm.2024.124902","DOIUrl":"10.1016/j.ijpharm.2024.124902","url":null,"abstract":"<div><div>A formerly developed mathematical model describing drug release from hydrophilic matrices (HMs) took into account resistance to drug release given by its dissolution and by the presence of a growing gel layer. Such a model was applied to previously reported release data obtained from HMs made of hydroxypropyl methylcellulose (HPMC), where acetaminophen was used as model drug and a cellulolytic product was added as “active” excipient to attain zero-order release kinetics. The Levich theory applied to acetaminophen intrinsic dissolution rate (IDR) data highlighted the suitability of such a drug for modeling purposes, given its good surface wettability. First assessment of the model ability to describe drug release from the abovementioned systems was carried out on partially coated matrices, representing a simplified physical frame, but results were then confirmed on uncoated systems. Experimental and model release data showed good agreement; therefore, the release-describing equation was combined with that of the global mass balance to obtain two new equations related to erosion and diffusion fronts time evolution. Changes over time in the dissolution and gel contributions to total resistance, calculated using model output parameters, highlighted that the enzyme, through its hydrolytic activity on HPMC, was responsible for a time-dependent reduction of the resistance component related to gel layer.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124902"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.ijpharm.2024.124921
Maria José Sánchez , Pablo Leivar , Salvador Borrós , Cristina Fornaguera , Martí Lecina
Extracellular Vesicles (EVs) are nanosized particles with significant role in disease pathogenesis and as therapeutic potential. However, the lack of reliable and efficient methods for the characterization, quantification and tracking of EVs, combined with the limitations of detection techniques in differentiating specific EVs subtypes with beneficial properties, makes these process complex and time-consuming. To address this challenge, EVs were engineered using a tricistronic plasmid that encodes fluorescent proteins fused to tetraspanins (eGFP-CD63 and mCherry-CD9), with both fluorophores localized within the luminal space. Double fluorescently labelled small EVs (sEVs) were then produced in a stably transfected HEK293SF-3F6 cell line. The fluorescently labelled sEVs were characterized using a variety of techniques. Protein expression analysis showed that the fused proteins were efficiently produced and incorporated in sEVs, as evidenced by clear fluorescence signal detected. Comparisons of the size distribution and concentration of modified sEVs with controls indicated that sEVs engineering did not affect their biogenesis and morphology. Fluorescently labelled sEVs were then quantified by flow cytometry, allowing to distinguish sEVs from other EVs subtypes or sample particles. The values were then compared to fluorometry measurements, obtaining a linear correlation what enabled a novel sEVs quantification method. The functionality of engineered sEVs was assessed by monitoring their uptake and trafficking in recipient cells, obtaining an efficient internalisation by target cells. Overall, these results demonstrate that the implementation of dual fluorescent methodology is feasible for sEVs characterization, quantification, for in vitro study of EVs interaction with cells, and intercellular communication, as well as a valuable tool in the in vitro development of targeted therapeutic EVs delivery systems.
{"title":"Enhanced quantification and cell tracking of dual fluorescent labeled extracellular vesicles","authors":"Maria José Sánchez , Pablo Leivar , Salvador Borrós , Cristina Fornaguera , Martí Lecina","doi":"10.1016/j.ijpharm.2024.124921","DOIUrl":"10.1016/j.ijpharm.2024.124921","url":null,"abstract":"<div><div>Extracellular Vesicles (EVs) are nanosized particles with significant role in disease pathogenesis and as therapeutic potential. However, the lack of reliable and efficient methods for the characterization, quantification and tracking of EVs, combined with the limitations of detection techniques in differentiating specific EVs subtypes with beneficial properties, makes these process complex and time-consuming. To address this challenge, EVs were engineered using a tricistronic plasmid that encodes fluorescent proteins fused to tetraspanins (eGFP-CD63 and mCherry-CD9), with both fluorophores localized within the luminal space. Double fluorescently labelled small EVs (sEVs) were then produced in a stably transfected HEK293SF-3F6 cell line. The fluorescently labelled sEVs were characterized using a variety of techniques. Protein expression analysis showed that the fused proteins were efficiently produced and incorporated in sEVs, as evidenced by clear fluorescence signal detected. Comparisons of the size distribution and concentration of modified sEVs with controls indicated that sEVs engineering did not affect their biogenesis and morphology. Fluorescently labelled sEVs were then quantified by flow cytometry, allowing to distinguish sEVs from other EVs subtypes or sample particles. The values were then compared to fluorometry measurements, obtaining a linear correlation what enabled a novel sEVs quantification method. The functionality of engineered sEVs was assessed by monitoring their uptake and trafficking in recipient cells, obtaining an efficient internalisation by target cells. Overall, these results demonstrate that the implementation of dual fluorescent methodology is feasible for sEVs characterization, quantification, <strong>for <em>in vitro</em></strong> study of EVs interaction with cells, and intercellular communication, as well as a valuable tool in the <strong><em>in vitro</em></strong> development of targeted therapeutic EVs delivery systems.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124921"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gold nanoparticles (AuNPs) have become a focus of interest in biomedicine due to their unique properties. By attaching peptides to these nanoparticles (NPs), they can be utilized for a wide range of applications. Peptides, which are short chains of amino acids, can be customized for specific molecular interactions, making them ideal for delivering AuNPs to particular cells or tissues. One of the peptide-AuNP-based bio-nano technological approaches involves targeted drug delivery. Including peptides as targeting agents, these NPs can be designed to bind to specific cell receptors or biomarkers. This allows for the direct delivery of therapeutic agents to diseased cells while minimizing unwanted side effects, improving the effectiveness of treatments. Additionally, peptide-functionalized AuNPs (PAuNPs) are crucial for imaging and diagnostics. By functionalizing the NPs with peptides that bind to specific molecular targets, such as cancer biomarkers, these NPs can be used to visualize diseased tissues. This enables the early detection of diseases and helps in determining the severity of conditions for better diagnosis and treatment outcomes. Moreover, PAuNPs have displayed promising potential in photothermal therapy. Once PAuNPs uptake and penetrate target cancer cells effectively, these NPs generate heat when exposed to specific wavelengths of light, efficiently eliminating tumors while preserving healthy surrounding tissues. Therefore, in this paper, we systematically review the potential of PAuNPs in various biomedical applications, including therapy and diagnosis, providing a future perspective.
{"title":"Biomedical applications of peptide-gold nanoarchitectonics","authors":"Samane Maghsoudian , Esmat Sajjadi , Niloufar Hadavi , Mobina Soltani , Zahra Karami , Alwan Abed Hamadi Al Qushawi , Mohammad Akrami , Farid Kalantari","doi":"10.1016/j.ijpharm.2024.124920","DOIUrl":"10.1016/j.ijpharm.2024.124920","url":null,"abstract":"<div><div>Gold nanoparticles (AuNPs) have become a focus of interest in biomedicine due to their unique properties. By attaching peptides to these nanoparticles (NPs), they can be utilized for a wide range of applications. Peptides, which are short chains of amino acids, can be customized for specific molecular interactions, making them ideal for delivering AuNPs to particular cells or tissues. One of the peptide-AuNP-based bio-nano technological approaches involves targeted drug delivery. Including peptides as targeting agents, these NPs can be designed to bind to specific cell receptors or biomarkers. This allows for the direct delivery of therapeutic agents to diseased cells while minimizing unwanted side effects, improving the effectiveness of treatments. Additionally, peptide-functionalized AuNPs (PAuNPs) are crucial for imaging and diagnostics. By functionalizing the NPs with peptides that bind to specific molecular targets, such as cancer biomarkers, these NPs can be used to visualize diseased tissues. This enables the early detection of diseases and helps in determining the severity of conditions for better diagnosis and treatment outcomes. Moreover, PAuNPs have displayed promising potential in photothermal therapy. Once PAuNPs uptake and penetrate target cancer cells effectively, these NPs generate heat when exposed to specific wavelengths of light, efficiently eliminating tumors while preserving healthy surrounding tissues. Therefore, in this paper, we systematically review the potential of PAuNPs in various biomedical applications, including therapy and diagnosis, providing a future perspective.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124920"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.ijpharm.2024.124913
Md Kamruzzaman , Helen Cathcart , Peter McLoughlin , Niall J. O’Reilly
Co-amorphous systems (CAMs) have shown promise in addressing the challenges associated with poorly water-soluble drugs. However, the limited selection of co-formers and the use of lab-scale techniques for their preparation present challenges in fully utilizing the advantages of CAMs. In this study, we used aspartame (a methyl ester of the aspartic acid/phenylalanine) as a model dipeptide with the BCS class II drug dipyridamole, to prepare co-amorphous systems using spray drying. The feed solutions were prepared by dissolving the drug and co-former into methanol–water mixtures. The spray drying process was evaluated and solid-state properties were compared with those of the individual amino acids, amino acid mixtures and aspartame as co-formers. Co-amorphous systems prepared with aspartame (AspPhe) exhibited better solid-state properties, including a higher glass transition temperature (Tg), compared to the individual amino acids and the mixture of amino acids. Additionally, this formulation showed improved physical stability when stored at 25 °C/60 % RH conditions. Hirshfeld Surface (HS) analysis was employed to visualize and analyse the molecular interaction sites within the crystal structures of dipyridamole and aspartame. The observed interactions were then correlated with the molecular interactions identified through FT-IR spectroscopic analysis within the CAMs. The spectroscopic analysis revealed molecular interactions between the sites found at the shortest distances in the HS analysis. The dominant hydrogen bond interactions identified in the co-amorphous DPM-AspPhe system was found to contribute significantly to its improve stability. X-ray powder diffraction in non-ambient mode reveals that both temperature and humidity play a role in the crystallization of the co-amorphous DPM-AspPhe. Crystallization rates increased notably at high temperature and humidity. To predict stability under accelerated conditions, the crystallization rates from DPM-AspPhe were fitted to a modified Arrhenius equation. However, the predictive accuracy of the resulting model was limited to a specific range of conditions.
{"title":"Evaluation of aspartame as a co-former in the preparation of co-amorphous formulations of dipyridamole using spray drying","authors":"Md Kamruzzaman , Helen Cathcart , Peter McLoughlin , Niall J. O’Reilly","doi":"10.1016/j.ijpharm.2024.124913","DOIUrl":"10.1016/j.ijpharm.2024.124913","url":null,"abstract":"<div><div>Co-amorphous systems (CAMs) have shown promise in addressing the challenges associated with poorly water-soluble drugs. However, the limited selection of co-formers and the use of lab-scale techniques for their preparation present challenges in fully utilizing the advantages of CAMs. In this study, we used aspartame (a methyl ester of the aspartic acid/phenylalanine) as a model dipeptide with the BCS class II drug dipyridamole, to prepare co-amorphous systems using spray drying. The feed solutions were prepared by dissolving the drug and co-former into methanol–water mixtures. The spray drying process was evaluated and solid-state properties were compared with those of the individual amino acids, amino acid mixtures and aspartame as co-formers. Co-amorphous systems prepared with aspartame (AspPhe) exhibited better solid-state properties, including a higher glass transition temperature (T<sub>g</sub>), compared to the individual amino acids and the mixture of amino acids. Additionally, this formulation showed improved physical stability when stored at 25 °C/60 % RH conditions. Hirshfeld Surface (HS) analysis was employed to visualize and analyse the molecular interaction sites within the crystal structures of dipyridamole and aspartame. The observed interactions were then correlated with the molecular interactions identified through FT-IR spectroscopic analysis within the CAMs. The spectroscopic analysis revealed molecular interactions between the sites found at the shortest distances in the HS analysis. The dominant hydrogen bond interactions identified in the co-amorphous DPM-AspPhe system was found to contribute significantly to its improve stability. X-ray powder diffraction in non-ambient mode reveals that both temperature and humidity play a role in the crystallization of the co-amorphous DPM-AspPhe. Crystallization rates increased notably at high temperature and humidity. To predict stability under accelerated conditions, the crystallization rates from DPM-AspPhe were fitted to a modified Arrhenius equation. However, the predictive accuracy of the resulting model was limited to a specific range of conditions.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124913"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.ijpharm.2024.124893
Sara A. Hassan , Marwa A. Zaater , Islam M. Abdel-Rahman , Elsayed A. Ibrahim , Ahmed M. El Kerdawy , Sara A. Abouelmagd
The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug. After screening a library of fourteen counterpart molecules, ten liquid PI-counterpart systems were developed and investigated. Thermal analysis confirmed the formation of IL/DES, while computational and spectroscopic studies revealed that hydrogen bonding played a crucial role in the interaction between PI and the counterparts, confirming DES formation. The solubility enhancement of PI in these systems ranged from ∼ 36 % to 294 %, with PI-Oxalic acid (OA) exhibiting the highest saturation solubility (49.71 μg/mL) and PI-Ibuprofen (IB) the lowest (17.23 μg/mL). The presence of hydrogen bonding groups in counterparts was key to successful DES formation. A negative correlation was observed between solubility and logP (r = − 0.75, p* = 0.0129), while a positive correlation was found between solubility and normalized polar surface area (PSA) (r = 0.68, p* = 0.029). PI-OA and PI-IB were located at the extreme ends of these regression lines, further validating the relationship between these properties and solubility enhancement. These findings highlight essential aspects of rational IL/DES design, optimizing their properties for broader applications.
{"title":"Piperine solubility enhancement via DES formation: Elucidation of intermolecular interactions and impact of counterpart structure via computational and spectroscopic approaches","authors":"Sara A. Hassan , Marwa A. Zaater , Islam M. Abdel-Rahman , Elsayed A. Ibrahim , Ahmed M. El Kerdawy , Sara A. Abouelmagd","doi":"10.1016/j.ijpharm.2024.124893","DOIUrl":"10.1016/j.ijpharm.2024.124893","url":null,"abstract":"<div><div>The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug. After screening a library of fourteen counterpart molecules, ten liquid PI-counterpart systems were developed and investigated. Thermal analysis confirmed the formation of IL/DES, while computational and spectroscopic studies revealed that hydrogen bonding played a crucial role in the interaction between PI and the counterparts, confirming DES formation. The solubility enhancement of PI in these systems ranged from ∼ 36 % to 294 %, with PI-Oxalic acid (OA) exhibiting the highest saturation solubility (49.71 μg/mL) and PI-Ibuprofen (IB) the lowest (17.23 μg/mL). The presence of hydrogen bonding groups in counterparts was key to successful DES formation. A negative correlation was observed between solubility and logP (r = − 0.75, p* = 0.0129), while a positive correlation was found between solubility and normalized polar surface area (PSA) (r = 0.68, p* = 0.029). PI-OA and PI-IB were located at the extreme ends of these regression lines, further validating the relationship between these properties and solubility enhancement. These findings highlight essential aspects of rational IL/DES design, optimizing their properties for broader applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124893"},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.ijpharm.2024.124915
Yue Shan, Yu Jin, Xiaoqi Zhang, Yufei Tang, Wenli Lai, Jinfeng Liao, Mengjie Wu, Hu Long
The prolonged duration of orthodontic treatment remains a significant concern for both orthodontists and patients. In this study, we developed a degradable microneedle (MN) patch composed of hyaluronic acid (HA) and sodium alginate (SA) for the delivery of receptor activator of nuclear factor-kappa B ligand (RANKL) to accelerate tooth movement. This MN patch which was crosslinked by calcium chloride (CaCl2) exhibits adequate mechanical properties and favorable in vitro mucosal insertion ability. Moreover, the MN patch can achieve the sustained release of RANKL and maintain the biological stability of RANKL protein after one month of storage at -20 °C, 4 °C, or 37 °C. In vitro experiments using RAW264.7 cells indicated that the HA/SA/RANKL MN possessed excellent biocompatibility and could effectively induce osteoclast differentiation. In vivo application of the HA/SA/RANKL MN in rat models showed a remarkable effect in promoting osteoclast formation and accelerating tooth movement. These findings suggest that the degradable HA/SA/RANKL MN holds significant potential for enhancing tooth movement efficiency.
{"title":"Development of a novel hyaluronic acid/alginate/RANKL degradable microneedle patch for accelerating bone remodeling and orthodontic tooth movement through promoting osteoclastogenesis.","authors":"Yue Shan, Yu Jin, Xiaoqi Zhang, Yufei Tang, Wenli Lai, Jinfeng Liao, Mengjie Wu, Hu Long","doi":"10.1016/j.ijpharm.2024.124915","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124915","url":null,"abstract":"<p><p>The prolonged duration of orthodontic treatment remains a significant concern for both orthodontists and patients. In this study, we developed a degradable microneedle (MN) patch composed of hyaluronic acid (HA) and sodium alginate (SA) for the delivery of receptor activator of nuclear factor-kappa B ligand (RANKL) to accelerate tooth movement. This MN patch which was crosslinked by calcium chloride (CaCl<sub>2</sub>) exhibits adequate mechanical properties and favorable in vitro mucosal insertion ability. Moreover, the MN patch can achieve the sustained release of RANKL and maintain the biological stability of RANKL protein after one month of storage at -20 °C, 4 °C, or 37 °C. In vitro experiments using RAW264.7 cells indicated that the HA/SA/RANKL MN possessed excellent biocompatibility and could effectively induce osteoclast differentiation. In vivo application of the HA/SA/RANKL MN in rat models showed a remarkable effect in promoting osteoclast formation and accelerating tooth movement. These findings suggest that the degradable HA/SA/RANKL MN holds significant potential for enhancing tooth movement efficiency.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124915"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.ijpharm.2024.124906
Jayanaraian F. Martins Andrade , Agnes-Valencia Weiss , Marcílio Cunha-Filho , Guilherme M. Gelfuso , Tais Gratieri , Marc Schneider
Hair follicles (HFs) represent a route of interest to drug delivery for treating several skin conditions. Iontophoresis, on the other hand, is a physical method to enhance drug permeation by applying a low electrical current to the formulation. HFs can be targeted following topical iontophoretic application, as they represent a pathway of lower electrical resistance, as well as a drug reservoir, in particular useful for nanoparticles (NPs), which can preferably accumulate in these structures. Combining both strategies may provide optimal results, but the literature still lacks evidence of the ideal NP characteristics for the iontophoretic drug delivery targeting the HFs. Here, we aimed to evaluate the effect of gelatin NPs’ size and charge under iontophoresis application on NPs’ deposition into the HFs. Four gelatin NP formulations were produced with varying gelatin concentrations and gelatin types (positively charged type A and negatively charged type B), with sizes ranging from 220 to 770 nm. A fluorescent dye, TRITC-dextran 150 kDa, was encapsulated for monitoring NPs deposition. Cutaneous penetration experiments were performed in vitro with and without iontophoresis for 6 h with pig ear skin. The deposition profile was assessed by confocal laser scanning microscopy. Photomicrographs showed a higher accumulation of the larger positively charged NPs (AL), reaching deeper portions of HFs, and showed iontophoresis further increased their deposition, resulting in the highest signal. In conclusion, these findings shed light on the applications of NPs and bring novel treatment opportunities for several diseases compromising the hair follicles.
{"title":"Effect of gelatin nanoparticles’ size and charge on iontophoretic targeted deposition to the hair follicles","authors":"Jayanaraian F. Martins Andrade , Agnes-Valencia Weiss , Marcílio Cunha-Filho , Guilherme M. Gelfuso , Tais Gratieri , Marc Schneider","doi":"10.1016/j.ijpharm.2024.124906","DOIUrl":"10.1016/j.ijpharm.2024.124906","url":null,"abstract":"<div><div>Hair follicles (HFs) represent a route of interest to drug delivery for treating several skin conditions. Iontophoresis, on the other hand, is a physical method to enhance drug permeation by applying a low electrical current to the formulation. HFs can be targeted following topical iontophoretic application, as they represent a pathway of lower electrical resistance, as well as a drug reservoir, in particular useful for nanoparticles (NPs), which can preferably accumulate in these structures. Combining both strategies may provide optimal results, but the literature still lacks evidence of the ideal NP characteristics for the iontophoretic drug delivery targeting the HFs. Here, we aimed to evaluate the effect of gelatin NPs’ size and charge under iontophoresis application on NPs’ deposition into the HFs. Four gelatin NP formulations were produced with varying gelatin concentrations and gelatin types (positively charged type A and negatively charged type B), with sizes ranging from 220 to 770 nm. A fluorescent dye, TRITC-dextran 150 kDa, was encapsulated for monitoring NPs deposition. Cutaneous penetration experiments were performed <em>in vitro</em> with and without iontophoresis for 6 h with pig ear skin. The deposition profile was assessed by confocal laser scanning microscopy. Photomicrographs showed a higher accumulation of the larger positively charged NPs (AL), reaching deeper portions of HFs, and showed iontophoresis further increased their deposition, resulting in the highest signal. In conclusion, these findings shed light on the applications of NPs and bring novel treatment opportunities for several diseases compromising the hair follicles.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124906"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.ijpharm.2024.124908
João Teixeira , Zélia Lumack do Monte , Sandra Tenreiro , Madalena Salema-Oom , Diana C. Silva , Benilde Saramago , Ana Paula Serro
Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with N-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained in vitro release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.
{"title":"Citicoline eluting hydrogels for therapeutic contact lenses intended to treat neurodegenerative diabetic ocular diseases","authors":"João Teixeira , Zélia Lumack do Monte , Sandra Tenreiro , Madalena Salema-Oom , Diana C. Silva , Benilde Saramago , Ana Paula Serro","doi":"10.1016/j.ijpharm.2024.124908","DOIUrl":"10.1016/j.ijpharm.2024.124908","url":null,"abstract":"<div><div>Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with <em>N</em>-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained <em>in vitro</em> release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124908"},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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