Pub Date : 2024-10-02DOI: 10.1016/j.ejpb.2024.114520
Hinpetch Daungsupawong , Viroj Wiwanitkit
{"title":"Dosage by design − 3D printing individualized cabozantinib tablets with immediate release: Correspondence","authors":"Hinpetch Daungsupawong , Viroj Wiwanitkit","doi":"10.1016/j.ejpb.2024.114520","DOIUrl":"10.1016/j.ejpb.2024.114520","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114520"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375339","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 : 2024-10-01DOI: 10.1016/j.ejpb.2024.114518
Anukrati Goel , Ruth Pendlington , Stephen Glavin , Tao Chen , Natalie A. Belsey
Understanding the mechanisms governing the penetration of substances into the skin is crucial for the development of safe and effective topical drug delivery systems and skincare products. This study examined the partitioning of model permeants into human skin, by assessing six substances with diverse logP values. We employed stimulated Raman scattering (SRS) microscopy, an ambient, label-free optical imaging technique known for its ability to provide chemical distribution with subcellular resolution. Our investigation assessed partitioning into the two primary pathways through which substances traverse the skin: the intercellular lipid matrix and the intracellular route via corneocyte cells. We observed that the partitioning behaviour was strongly influenced by the lipophilicity of the molecule, with lipophilic compounds showing greater affinity for intercellular matrix with increased lipophilicity. Conversely, hydrophilic molecules demonstrated a preference for corneocyte cells, with their affinity increasing with increased hydrophilicity. The findings contribute to our understanding of the mechanisms underlying topical delivery and offer important implications and new methods beneficial for the development of safe and effective topical products. In addition, the methods presented could be valuable to reveal changes in drug partitioning or to assess targeting approaches in diseased skin models.
{"title":"Characterisation of skin penetration pathways using stimulated Raman scattering microscopy","authors":"Anukrati Goel , Ruth Pendlington , Stephen Glavin , Tao Chen , Natalie A. Belsey","doi":"10.1016/j.ejpb.2024.114518","DOIUrl":"10.1016/j.ejpb.2024.114518","url":null,"abstract":"<div><div>Understanding the mechanisms governing the penetration of substances into the skin is crucial for the development of safe and effective topical drug delivery systems and skincare products. This study examined the partitioning of model permeants into human skin, by assessing six substances with diverse logP values. We employed stimulated Raman scattering (SRS) microscopy, an ambient, label-free optical imaging technique known for its ability to provide chemical distribution with subcellular resolution. Our investigation assessed partitioning into the two primary pathways through which substances traverse the skin: the intercellular lipid matrix and the intracellular route via corneocyte cells. We observed that the partitioning behaviour was strongly influenced by the lipophilicity of the molecule, with lipophilic compounds showing greater affinity for intercellular matrix with increased lipophilicity. Conversely, hydrophilic molecules demonstrated a preference for corneocyte cells, with their affinity increasing with increased hydrophilicity. The findings contribute to our understanding of the mechanisms underlying topical delivery and offer important implications and new methods beneficial for the development of safe and effective topical products. In addition, the methods presented could be valuable to reveal changes in drug partitioning or to assess targeting approaches in diseased skin models.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114518"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371364","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}
Antimicrobial resistance (AMR) has emerged as a significant threat to human health. Antimicrobial peptides (AMPs) have proven to be an effective strategy against antibiotic-resistant bacteria, given their capacity to swiftly disrupt microorganism membranes and alter cell morphology. A common limitation, however, lies in the inherent toxicity of many AMPs and their vulnerability to protease degradation within the body. Photothermal therapy (PTT) stands out as a widely utilized approach in combating antibiotic-resistant bacterial infections, boasting high efficiency and non-invasive benefits. To enhance the stability and antibacterial efficacy of AMPs, a novel approach involving the combination of AMPs and PTT has been proposed. This study focuses on the encapsulation of At10 (an AMP designed by our group), and copper sulfide nanoparticles (CuS NPs) within zeolitic imidazolate framework-8 (ZIF-8) to form nanocomposites (At10/CuS@ZIF-8). The encapsulated CuS NPs exhibit notable photothermal properties upon exposure to near-infrared radiation. This induces the cleavage of ZIF-8, facilitating the release of At10, which effectively targets bacterial membranes to exert its antibacterial effects. Bacteria treated with At10/CuS@ZIF-8 under light radiation exhibited not only membrane folding and intracellular matrix outflow but also bacterial fracture. This synergistic antibacterial strategy, integrating the unique properties of AMPs, CuS NPs, and pH responsiveness of ZIF-8, holds promising potential for widespread application in the treatment of bacterial infections.
{"title":"Synergistic bactericidal effect of antimicrobial peptides and copper sulfide-loaded zeolitic imidazolate framework-8 nanoparticles with photothermal therapy","authors":"Duoduo Zhang , Shiyue Bie , Mhd Anas Tomeh , Xinyu Zhang , Xiubo Zhao","doi":"10.1016/j.ejpb.2024.114516","DOIUrl":"10.1016/j.ejpb.2024.114516","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) has emerged as a significant threat to human health. Antimicrobial peptides (AMPs) have proven to be an effective strategy against antibiotic-resistant bacteria, given their capacity to swiftly disrupt microorganism membranes and alter cell morphology. A common limitation, however, lies in the inherent toxicity of many AMPs and their vulnerability to protease degradation within the body. Photothermal therapy (PTT) stands out as a widely utilized approach in combating antibiotic-resistant bacterial infections, boasting high efficiency and non-invasive benefits. To enhance the stability and antibacterial efficacy of AMPs, a novel approach involving the combination of AMPs and PTT has been proposed. This study focuses on the encapsulation of At10 (an AMP designed by our group), and copper sulfide nanoparticles (CuS NPs) within zeolitic imidazolate framework-8 (ZIF-8) to form nanocomposites (At10/CuS@ZIF-8). The encapsulated CuS NPs exhibit notable photothermal properties upon exposure to near-infrared radiation. This induces the cleavage of ZIF-8, facilitating the release of At10, which effectively targets bacterial membranes to exert its antibacterial effects. Bacteria treated with At10/CuS@ZIF-8 under light radiation exhibited not only membrane folding and intracellular matrix outflow but also bacterial fracture. This synergistic antibacterial strategy, integrating the unique properties of AMPs, CuS NPs, and pH responsiveness of ZIF-8, holds promising potential for widespread application in the treatment of bacterial infections.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114516"},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344201","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 : 2024-09-28DOI: 10.1016/j.ejpb.2024.114517
Laura Koenitz, Abina Crean, Sonja Vucen
Protein therapeutics are essential in the treatment of various diseases, but most of them require parenteral administration. Since intravenous and subcutaneous injections are associated with discomfort and pain, other routes have been investigated including intradermal microneedle delivery. Microneedles are shorter than hypodermic needles and therefore minimize contact with pain receptors in deeper skin layers. But the differences in anatomical and physiological characteristics of dermis and subcutis can potentially result in varying protein penetration through the skin, absorption, and metabolism. This review summarizes pharmacokinetic studies that compare the administration of protein therapeutics by subcutaneous injections and different types of microneedles intradermally including hollow, dissolvable, coated, and hydrogel-forming microneedles. Across animal and human studies, hollow microneedle delivery resulted in quicker and higher peak plasma levels of proteins and comparable bioavailability to subcutaneous injections potentially due to the extensive network of lymphatic and blood vessels in the dermis. In case of dissolvable and coated microneedles, drug release kinetics depend on component materials. The dissolution of polymer excipients can slow the release and permeation of protein therapeutics at the administration site and thereby delay absorption. The understanding of drug penetration through different skin layers, its absorption into blood capillaries or lymphatics, and dermal metabolism remains limited. Additionally, the effects of these processes on the differences in pharmacokinetic profiles of proteins following intradermal microneedle administration are not well understood. Greater insights are required for the development of the next generation of intradermal microneedle biotherapeutics.
{"title":"Pharmacokinetic differences between subcutaneous injection and intradermal microneedle delivery of protein therapeutics","authors":"Laura Koenitz, Abina Crean, Sonja Vucen","doi":"10.1016/j.ejpb.2024.114517","DOIUrl":"10.1016/j.ejpb.2024.114517","url":null,"abstract":"<div><div>Protein therapeutics are essential in the treatment of various diseases, but most of them require parenteral administration. Since intravenous and subcutaneous injections are associated with discomfort and pain, other routes have been investigated including intradermal microneedle delivery. Microneedles are shorter than hypodermic needles and therefore minimize contact with pain receptors in deeper skin layers. But the differences in anatomical and physiological characteristics of dermis and subcutis can potentially result in varying protein penetration through the skin, absorption, and metabolism. This review summarizes pharmacokinetic studies that compare the administration of protein therapeutics by subcutaneous injections and different types of microneedles intradermally including hollow, dissolvable, coated, and hydrogel-forming microneedles. Across animal and human studies, hollow microneedle delivery resulted in quicker and higher peak plasma levels of proteins and comparable bioavailability to subcutaneous injections potentially due to the extensive network of lymphatic and blood vessels in the dermis. In case of dissolvable and coated microneedles, drug release kinetics depend on component materials. The dissolution of polymer excipients can slow the release and permeation of protein therapeutics at the administration site and thereby delay absorption. The understanding of drug penetration through different skin layers, its absorption into blood capillaries or lymphatics, and dermal metabolism remains limited. Additionally, the effects of these processes on the differences in pharmacokinetic profiles of proteins following intradermal microneedle administration are not well understood. Greater insights are required for the development of the next generation of intradermal microneedle biotherapeutics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114517"},"PeriodicalIF":4.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344200","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}
Therapeutic proteins suffer from physical and chemical instability in aqueous solution. Polysorbates and poloxamers are often added for protection against interfacial stress to prevent protein aggregation and particle formation. Previous studies have revealed that the hydrolysis and oxidation of polysorbates in parenteral formulations can lead to the formation of free fatty acid particles, insufficient long-term stabilization, and protein oxidation. Poloxamers, on the other hand, are considered to be less effective against protein aggregation. Here we investigated two lyso-phosphatidylcholines (LPCs) as potential alternative surfactants for protein formulations, focusing on their physicochemical behavior and their ability to protect against the formation of monoclonal antibody particles during mechanical stress.
The hemolytic activity of LPC was tested in varying ratios of plasma and buffer mixtures. LPC effectively stabilized mAb formulations when shaken at concentrations several orders of magnitude below the onset of hemolysis, indicating that the potential for erythrocyte damage by LPC is non-critical. LPC formulations subjected to mechanical stress through peristaltic pumping exhibited comparable protein particle formation to those containing polysorbate 80 or poloxamer 188. Profile analysis tensiometry and dilatational rheology indicated that the stabilizing effect likely arises from the formation of a viscoelastic film at approximately the CMC. Data gathered from concentration-gradient multi-angle light scattering and isothermal titration calorimetry support this finding. Surfactant desorption was evaluated through sub-phase exchange experiments. While LPCs readily desorbed from the interface, resorption occurred rapidly enough in the bulk solution to prevent protein adsorption. Overall, LPCs behave similarly to polysorbate with respect to interfacial stabilization and show promise as a potential substitute for polysorbate in parenteral protein formulations.
{"title":"Lyso-phosphatidylcholine as an interfacial stabilizer for parenteral monoclonal antibody formulations","authors":"Eleni Papadopoulos , Betharie Cendera Arrahmani , Katharina Beck , Wolfgang Friess","doi":"10.1016/j.ejpb.2024.114514","DOIUrl":"10.1016/j.ejpb.2024.114514","url":null,"abstract":"<div><div>Therapeutic proteins suffer from physical and chemical instability in aqueous solution. Polysorbates and poloxamers are often added for protection against interfacial stress to prevent protein aggregation and particle formation. Previous studies have revealed that the hydrolysis and oxidation of polysorbates in parenteral formulations can lead to the formation of free fatty acid particles, insufficient long-term stabilization, and protein oxidation. Poloxamers, on the other hand, are considered to be less effective against protein aggregation. Here we investigated two lyso-phosphatidylcholines (LPCs) as potential alternative surfactants for protein formulations, focusing on their physicochemical behavior and their ability to protect against the formation of monoclonal antibody particles during mechanical stress.</div><div>The hemolytic activity of LPC was tested in varying ratios of plasma and buffer mixtures. LPC effectively stabilized mAb formulations when shaken at concentrations several orders of magnitude below the onset of hemolysis, indicating that the potential for erythrocyte damage by LPC is non-critical. LPC formulations subjected to mechanical stress through peristaltic pumping exhibited comparable protein particle formation to those containing polysorbate 80 or poloxamer 188. Profile analysis tensiometry and dilatational rheology indicated that the stabilizing effect likely arises from the formation of a viscoelastic film at approximately the CMC. Data gathered from concentration-gradient multi-angle light scattering and isothermal titration calorimetry support this finding. Surfactant desorption was evaluated through sub-phase exchange experiments. While LPCs readily desorbed from the interface, resorption occurred rapidly enough in the bulk solution to prevent protein adsorption. Overall, LPCs behave similarly to polysorbate with respect to interfacial stabilization and show promise as a potential substitute for polysorbate in parenteral protein formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114514"},"PeriodicalIF":4.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344199","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 : 2024-09-26DOI: 10.1016/j.ejpb.2024.114512
Salma M. Abdel-Hafez , Markus Gallei , Sylvia Wagner , Marc Schneider
The use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents. To this end, the aim of the current work is to develop an ECM-modulating nano-structured microparticulate carrier, that not only enables the delivery of therapeutic nanoparticles (NPs) to the lungs, but also enhances their intratumoral penetration. The system is composed of acetalated maltodextrin (AcMD) NPs embedded into a water-soluble trehalose/leucine matrix, in which collagenase was loaded with different mass concentrations (10 %, 30 % and 50 %). The collagenase-containing AcMD nano-structured microparticles (MPs) exhibited suitable median volume diameters (2.58 ± 1.35 to 3.01 ± 0.68 µm), hollow corrugated morphology, sufficient redispersibility, low residual moisture content (2.71 ± 0.17 % to 3.10 ± 0.20 %), and favorable aerodynamic properties (Mass median aerodynamic diameter (MMAD): 1.93 ± 0.06 to 2.80 ± 0.10 µm and fine particle fraction (FPF): 68.02 ± 6.86 % to 69.62 ± 2.01 %). Importantly, collagenase retained as high as 89.5 ± 6.7 % of its enzymatic activity after spray drying. MPs containing 10 % mass content of collagenase did not show signs of cytotoxicity on either human lung adenocarcinoma A549 cells or lung MRC-5 fibroblasts. The nanoparticle penetration was tested using adenocarcinoma A549/MRC-5 co-culture spheroid model, where the inclusion of collagenase resulted in deeper penetration depth of AcMD-NPs.
{"title":"Inhalable nano-structured microparticles for extracellular matrix modulation as a potential delivery system for lung cancer","authors":"Salma M. Abdel-Hafez , Markus Gallei , Sylvia Wagner , Marc Schneider","doi":"10.1016/j.ejpb.2024.114512","DOIUrl":"10.1016/j.ejpb.2024.114512","url":null,"abstract":"<div><div>The use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents. To this end, the aim of the current work is to develop an ECM-modulating nano-structured microparticulate carrier, that not only enables the delivery of therapeutic nanoparticles (NPs) to the lungs, but also enhances their intratumoral penetration. The system is composed of acetalated maltodextrin (AcMD) NPs embedded into a water-soluble trehalose/leucine matrix, in which collagenase was loaded with different mass concentrations (10 %, 30 % and 50 %). The collagenase-containing AcMD nano-structured microparticles (MPs) exhibited suitable median volume diameters (2.58 ± 1.35 to 3.01 ± 0.68 µm), hollow corrugated morphology, sufficient redispersibility, low residual moisture content (2.71 ± 0.17 % to 3.10 ± 0.20 %), and favorable aerodynamic properties (Mass median aerodynamic diameter (MMAD): 1.93 ± 0.06 to 2.80 ± 0.10 µm and fine particle fraction (FPF): 68.02 ± 6.86 % to 69.62 ± 2.01 %). Importantly, collagenase retained as high as 89.5 ± 6.7 % of its enzymatic activity after spray drying. MPs containing 10 % mass content of collagenase did not show signs of cytotoxicity on either human lung adenocarcinoma A549 cells or lung MRC-5 fibroblasts. The nanoparticle penetration was tested using adenocarcinoma A549/MRC-5 co-culture spheroid model, where the inclusion of collagenase resulted in deeper penetration depth of AcMD-NPs.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114512"},"PeriodicalIF":4.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344198","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 : 2024-09-24DOI: 10.1016/j.ejpb.2024.114515
Florian Kias, Roland Bodmeier
The removal of organic solvents during the preparation of biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by an O/W- solvent extraction/evaporation process was investigated and controlled by diafiltration. Emulsification and steady replacement of the aqueous phase were performed in parallel in a single-vessel setup. During the process, the solidification of the dispersed phase (drug:PLGA:solvent droplets) into microparticles was monitored with video-microscopy and focused beam reflectance measurement (FBRM) and the residual solvent content was analyzed with headspace gas chromatography (organic solvent) and coulometric Karl-Fischer titration (water). Microparticles containing dexamethasone or risperidone were characterized with regard to particle size, morphology, encapsulation efficiency and in-vitro release. Diafiltration-accelerated solvent extraction shortened the process time by accelerating solidification of dispersed phase but reduced the residual dichloromethane content only in combination with increased temperature. Increasing the diafiltration rate increased particle size, porosity, and the encapsulation efficiency of risperidone. The latter effect was particularly evident with increasing lipophilicity of PLGA. A slower and more uniform solidification of end-capped and increased lactide content PLGA grade was identified as the reason for an increased drug leaching. Accelerated solvent extraction by diafiltration did not affect the in-vitro release of risperidone from different PLGA grades. The initial burst release of dexamethasone was increased by diafiltration when encapsulated in concentrations above the percolation threshold. Both porosity and burst release could be reduced by increasing the process temperature during diafiltration. Residual water content was established as an indicator for porosity and correlated with the burst release of dexamethasone.
{"title":"Control of encapsulation efficiency and morphology of poly(lactide-co-glycolide) microparticles with a diafiltration-driven solvent extraction process","authors":"Florian Kias, Roland Bodmeier","doi":"10.1016/j.ejpb.2024.114515","DOIUrl":"10.1016/j.ejpb.2024.114515","url":null,"abstract":"<div><div>The removal of organic solvents during the preparation of biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by an O/W- solvent extraction/evaporation process was investigated and controlled by diafiltration. Emulsification and steady replacement of the aqueous phase were performed in parallel in a single-vessel setup. During the process, the solidification of the dispersed phase (drug:PLGA:solvent droplets) into microparticles was monitored with video-microscopy and focused beam reflectance measurement (FBRM) and the residual solvent content was analyzed with headspace gas chromatography (organic solvent) and coulometric Karl-Fischer titration (water). Microparticles containing dexamethasone or risperidone were characterized with regard to particle size, morphology, encapsulation efficiency and in-vitro release. Diafiltration-accelerated solvent extraction shortened the process time by accelerating solidification of dispersed phase but reduced the residual dichloromethane content only in combination with increased temperature. Increasing the diafiltration rate increased particle size, porosity, and the encapsulation efficiency of risperidone. The latter effect was particularly evident with increasing lipophilicity of PLGA. A slower and more uniform solidification of end-capped and increased lactide content PLGA grade was identified as the reason for an increased drug leaching. Accelerated solvent extraction by diafiltration did not affect the in-vitro release of risperidone from different PLGA grades. The initial burst release of dexamethasone was increased by diafiltration when encapsulated in concentrations above the percolation threshold. Both porosity and burst release could be reduced by increasing the process temperature during diafiltration. Residual water content was established as an indicator for porosity and correlated with the burst release of dexamethasone.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114515"},"PeriodicalIF":4.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327957","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 : 2024-09-21DOI: 10.1016/j.ejpb.2024.114510
Kunal Pednekar , Julia Minnee , I. Jolanda M. de Vries , Jai Prakash
Tumor-associated innate immune cells such as tumor-associated macrophages, neutrophils, dendritic cells play a crucial role in tumor progression, angiogenesis and metastasis. These cells also control the efficacy of chemotherapy and immunotherapy by inducing drug resistance and immunosuppression, leading to therapeutic failures. Therefore, targeting the tumor-associated innate immune cells has gained high attention for the development of effective cancer therapy. Nanomedicine based strategies to target these cells are highly relevant and can be used to reprogram these cells. In this review, we discuss the fundamental roles of the tumor-associated innate immune cells in the tumor microenvironment and different strategies to modulate them. Then, nanomedicine-based strategies to target different tumor innate immune cells are explained in detail. While the clinical development of the targeted nanomedicine remains a great challenge in practice, we have provided our perspectives on various factors such as pharmaceutical aspects, preclinical testing and biological aspects which are crucial to consider before translating these targeting strategies to clinics.
{"title":"Targeted nanomedicine for reprogramming the tumor innate immune system: From bench to bedside","authors":"Kunal Pednekar , Julia Minnee , I. Jolanda M. de Vries , Jai Prakash","doi":"10.1016/j.ejpb.2024.114510","DOIUrl":"10.1016/j.ejpb.2024.114510","url":null,"abstract":"<div><div>Tumor-associated innate immune cells such as tumor-associated macrophages, neutrophils, dendritic cells play a crucial role in tumor progression, angiogenesis and metastasis. These cells also control the efficacy of chemotherapy and immunotherapy by inducing drug resistance and immunosuppression, leading to therapeutic failures. Therefore, targeting the tumor-associated innate immune cells has gained high attention for the development of effective cancer therapy. Nanomedicine based strategies to target these cells are highly relevant and can be used to reprogram these cells. In this review, we discuss the fundamental roles of the tumor-associated innate immune cells in the tumor microenvironment and different strategies to modulate them. Then, nanomedicine-based strategies to target different tumor innate immune cells are explained in detail. While the clinical development of the targeted nanomedicine remains a great challenge in practice, we have provided our perspectives on various factors such as pharmaceutical aspects, preclinical testing and biological aspects which are crucial to consider before translating these targeting strategies to clinics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114510"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003369/pdfft?md5=baf55c0d03e6c3f5760d693726475ee8&pid=1-s2.0-S0939641124003369-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282535","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 : 2024-09-21DOI: 10.1016/j.ejpb.2024.114513
Isaïe Nyamba , Charles B Sombié , Moussa Yabré , Hermine Zimé-Diawara , Josias Yaméogo , Salfo Ouédraogo , Anna Lechanteur , Rasmané Semdé , Brigitte Evrard
High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility. Undoubtedly, the issue of poorly water-soluble medications has been progressively escalating over recent years. Indeed, 40% of the top 200 oral medications marketed in the United States, 33% of drugs listed in the US pharmacopoeia, 75% of compounds under development and 90% of new chemical entities are insufficiently water-soluble compounds. In order to address this obstacle, formulation scientists employ a variety of approaches, encompassing both physical and chemical methods such as prodrug synthesis, salt formation, solid dispersions formation, hydrotropic substances utilization, solubilizing agents incorporation, cosolvent addition, polymorphism exploration, cocrystal creation, cyclodextrins complexation, lipid formulations, particle size reduction and nanoformulation techniques. Despite the utilization of these diverse approaches, the primary reason for the failure in new drug development persists as the poor aqueous solubility of pharmaceutical compounds. This paper, therefore, delves into the foundational principles that underpin the implementation of various formulation strategies, along with a discussion on the respective advantages and drawbacks associated with each approach. Additionally, a discourse is provided regarding methodological frameworks for making informed decisions on selecting an appropriate formulation strategy to effectively tackle the key challenges posed during the development of a poorly water-soluble drug candidate.
{"title":"Pharmaceutical approaches for enhancing solubility and oral bioavailability of poorly soluble drugs","authors":"Isaïe Nyamba , Charles B Sombié , Moussa Yabré , Hermine Zimé-Diawara , Josias Yaméogo , Salfo Ouédraogo , Anna Lechanteur , Rasmané Semdé , Brigitte Evrard","doi":"10.1016/j.ejpb.2024.114513","DOIUrl":"10.1016/j.ejpb.2024.114513","url":null,"abstract":"<div><div>High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility. Undoubtedly, the issue of poorly water-soluble medications has been progressively escalating over recent years. Indeed, 40% of the top 200 oral medications marketed in the United States, 33% of drugs listed in the US pharmacopoeia, 75% of compounds under development and 90% of new chemical entities are insufficiently water-soluble compounds. In order to address this obstacle, formulation scientists employ a variety of approaches, encompassing both physical and chemical methods such as prodrug synthesis, salt formation, solid dispersions formation, hydrotropic substances utilization, solubilizing agents incorporation, cosolvent addition, polymorphism exploration, cocrystal creation, cyclodextrins complexation, lipid formulations, particle size reduction and nanoformulation techniques. Despite the utilization of these diverse approaches, the primary reason for the failure in new drug development persists as the poor aqueous solubility of pharmaceutical compounds. This paper, therefore, delves into the foundational principles that underpin the implementation of various formulation strategies, along with a discussion on the respective advantages and drawbacks associated with each approach. Additionally, a discourse is provided regarding methodological frameworks for making informed decisions on selecting an appropriate formulation strategy to effectively tackle the key challenges posed during the development of a poorly water-soluble drug candidate.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114513"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307390","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 : 2024-09-21DOI: 10.1016/j.ejpb.2024.114511
Yinlian Yao , Shilong Fan , Yinqiang Fan , Xin Shen , Xingxing Chai , Jiang Pi , Xueqin Huang , Yiming Shao , Zhikun Zhou , Yue Zhao , Hua Jin
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.
{"title":"Intratracheal delivery of macrophage targeted Celastrol-loaded PLGA nanoparticles for enhanced anti-inflammatory efficacy in acute lung injury mice","authors":"Yinlian Yao , Shilong Fan , Yinqiang Fan , Xin Shen , Xingxing Chai , Jiang Pi , Xueqin Huang , Yiming Shao , Zhikun Zhou , Yue Zhao , Hua Jin","doi":"10.1016/j.ejpb.2024.114511","DOIUrl":"10.1016/j.ejpb.2024.114511","url":null,"abstract":"<div><div>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. <em>In vitro</em> data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. <em>In vivo</em> experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114511"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282518","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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