Pub Date : 2025-02-22DOI: 10.1016/j.ijpharm.2025.125389
Lucas Chiarentin , Vera Moura , Carla Vitorino
This study outlines a framework for developing a texture analyzer-based mucoadhesion method integrated with rheology analysis for evaluating ointment formulations. Using an Analytical Quality by Design (AQbD) approach, key sources of variability affecting critical method variables (CMVs) were identified. A Box-Behnken design evaluated applied force, contact time, and trigger force, with optimal conditions selected via response surface methodology (RSM) within the method operable design region (MODR). The final conditions—2 N applied force, 60 s contact time, and 0.05 N trigger force—ensured compliance with the analytical target profile (ATP). Incorporating mucin dispersion revealed significant rheological synergism, validating the optimized method. The framework adheres to ICH guidelines, demonstrating robust and reproducible performance.
{"title":"Mucoadhesion and rheology characterization in topical semisolid formulations: An AQbD-driven case study","authors":"Lucas Chiarentin , Vera Moura , Carla Vitorino","doi":"10.1016/j.ijpharm.2025.125389","DOIUrl":"10.1016/j.ijpharm.2025.125389","url":null,"abstract":"<div><div>This study outlines a framework for developing a texture analyzer-based mucoadhesion method integrated with rheology analysis for evaluating ointment formulations. Using an Analytical Quality by Design (AQbD) approach, key sources of variability affecting critical method variables (CMVs) were identified. A Box-Behnken design evaluated applied force, contact time, and trigger force, with optimal conditions selected via response surface methodology (RSM) within the method operable design region (MODR). The final conditions—2 N applied force, 60 s contact time, and 0.05 N trigger force—ensured compliance with the analytical target profile (ATP). Incorporating mucin dispersion revealed significant rheological synergism, validating the optimized method. The framework adheres to ICH guidelines, demonstrating robust and reproducible performance.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125389"},"PeriodicalIF":5.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491942","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 : 2025-02-22DOI: 10.1016/j.ijpharm.2025.125393
S. Pisani , A. Piazza , R. Dorati , I. Genta , M. Rosalia , E. Chiesa , G. Bruni , R. Migliavacca , B. Conti
Goal of this study is to apply electrospinning technology for manufacturing polymeric drug delivery systems with thermal sensitive shape memory behaviour. The hypothesis is to obtain electrospun patches loaded with an antibiotic drug to be implanted into the human body by minimal invasive technique, as local anti-infective therapy for surgical site infections treatment. Polylactide-co-polycaprolactone 70:30 (PLLA-co-PCL 70:30) was selected as temperature responsive polymer due to its Tg° value (32–42 °C) in the range of body temperature. Gentamicin (GS) was selected because used in last-line therapy against multidrug-resistant bacteria with several side effects upon its systemic administration.
After been manufactured, the electrospun patches underwent thermalshape memory thermal treatment (SMT) applying different thermal conditions and they were characterized before and after SMT by SEM, DSC, mechanical testing and antibacterial effect on S. Aureus clinical strains.
The results show that shape memory property of PLLA-co-PCL 70:30 patches is maintained both after GS loading and SMT at 60 °C that did not affect both nanofiber morphology and drug release. A change in copolymer conformation due to electrospinning occurs and GS loading, as highlighted by changes in patches thermal behaviour. The matrices mechanical properties address their application to internal surgical wounds, mainly soft tissues. Patches antimicrobial effect gave promising positive results for Gentamicin-susceptible strains, including a clinical isolate.
{"title":"Investigating electrospun shape memory patches as Gentamicin drug delivery system","authors":"S. Pisani , A. Piazza , R. Dorati , I. Genta , M. Rosalia , E. Chiesa , G. Bruni , R. Migliavacca , B. Conti","doi":"10.1016/j.ijpharm.2025.125393","DOIUrl":"10.1016/j.ijpharm.2025.125393","url":null,"abstract":"<div><div>Goal of this study is to apply electrospinning technology for manufacturing polymeric drug delivery systems with thermal sensitive shape memory behaviour. The hypothesis is to obtain electrospun patches loaded with an antibiotic drug to be implanted into the human body by minimal invasive technique, as local anti-infective therapy for surgical site infections treatment. Polylactide-co-polycaprolactone 70:30 (PLLA-co-PCL 70:30) was selected as temperature responsive polymer due to its Tg° value (32–42 °C) in the range of body temperature. Gentamicin (GS) was selected because used in last-line therapy against multidrug-resistant bacteria with several side effects upon its systemic administration.</div><div>After been manufactured, the electrospun patches underwent thermalshape memory thermal treatment (SMT) applying different thermal conditions and they were characterized before and after SMT by SEM, DSC, mechanical testing and antibacterial effect on <em>S. Aureus</em> clinical strains.</div><div>The results show that shape memory property of PLLA-co-PCL 70:30 patches is maintained both after GS loading and SMT at 60 °C that did not affect both nanofiber morphology and drug release. A change in copolymer conformation due to electrospinning occurs and GS loading, as highlighted by changes in patches thermal behaviour. The matrices mechanical properties address their application to internal surgical wounds, mainly soft tissues. Patches antimicrobial effect gave promising positive results for Gentamicin-susceptible strains, including a clinical isolate.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125393"},"PeriodicalIF":5.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491939","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 : 2025-02-22DOI: 10.1016/j.ijpharm.2025.125383
Md Hridoy , Irfan Khan , Mercy Ramanjulu , Paul Anthony , Wayne Childers , Swati Nagar , Ken Korzekwa
Passive permeability through biological membranes requires partitioning of drug molecules into the lipid bilayer and subsequent permeation. Most drugs are weak acids or bases, making their ionization constants (pKa) critical for predicting permeation across biological barriers. The pH-partition hypothesis posits that only the uncharged form contributes to passive permeability, suggesting a proportional relationship between permeability and uncharged fraction. However, experimental pH-permeability profiles are not accurately predicted with neutral fractions calculated using aqueous pKa values. Interactions between charged solutes and phospholipids are expected to alter the pKa of drugs within the membrane. In this study, we use modeling and simulation and experimental partitioning in a biphasic surrogate phospholipid membrane system, diacetyl phosphatidylcholine (DAcPC) and n-hexane, to study pH dependent permeability. Models were constructed in which pKa values were either shifted or distributed around the aqueous pKa and the resulting neutral fractions were compared to pH-dependent permeabilities. For acids, models with shifted or distributed pKa values can explain pH-dependent permeabilities in Caco-2 cells, but these models were not predictive for bases. For partitioning studies, five probe drugs, two acidic (ketoprofen, tolbutamide), two basic (metoprolol, verapamil), and one neutral (diazepam), were partitioned between n-hexane and buffer or buffer-hydrated DAcPC at different pH values. The apparent pKa values in the surrogate phospholipid system (C6/DAcPC) were shifted from their aqueous pKa values. However, the resulting pKa values did not predict observed pH-dependent Caco-2 permeabilities. Models that decrease the pH-pKa difference improve permeability predictions for both bases and acids and use of a pKa shift or distribution can further improve predictions for acids.
{"title":"Mechanistic studies on pH-permeability relationships: Impact of the membrane polar headgroup region on pKa","authors":"Md Hridoy , Irfan Khan , Mercy Ramanjulu , Paul Anthony , Wayne Childers , Swati Nagar , Ken Korzekwa","doi":"10.1016/j.ijpharm.2025.125383","DOIUrl":"10.1016/j.ijpharm.2025.125383","url":null,"abstract":"<div><div>Passive permeability through biological membranes requires partitioning of drug molecules into the lipid bilayer and subsequent permeation. Most drugs are weak acids or bases, making their ionization constants (pK<sub>a</sub>) critical for predicting permeation across biological barriers. The pH-partition hypothesis posits that only the uncharged form contributes to passive permeability, suggesting a proportional relationship between permeability and uncharged fraction. However, experimental pH-permeability profiles are not accurately predicted with neutral fractions calculated using aqueous pK<sub>a</sub> values. Interactions between charged solutes and phospholipids are expected to alter the pK<sub>a</sub> of drugs within the membrane. In this study, we use modeling and simulation and experimental partitioning in a biphasic surrogate phospholipid membrane system, diacetyl phosphatidylcholine (DAcPC) and n-hexane, to study pH dependent permeability. Models were constructed in which pK<sub>a</sub> values were either shifted or distributed around the aqueous pK<sub>a</sub> and the resulting neutral fractions were compared to pH-dependent permeabilities. For acids, models with shifted or distributed pK<sub>a</sub> values can explain pH-dependent permeabilities in Caco-2 cells, but these models were not predictive for bases. For partitioning studies, five probe drugs, two acidic (ketoprofen, tolbutamide), two basic (metoprolol, verapamil), and one neutral (diazepam), were partitioned between n-hexane and buffer or buffer-hydrated DAcPC at different pH values. The apparent pK<sub>a</sub> values in the surrogate phospholipid system (C6/DAcPC) were shifted from their aqueous pK<sub>a</sub> values. However, the resulting pK<sub>a</sub> values did not predict observed pH-dependent Caco-2 permeabilities. Models that decrease the pH-pK<sub>a</sub> difference improve permeability predictions for both bases and acids and use of a pK<sub>a</sub> shift or distribution can further improve predictions for acids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125383"},"PeriodicalIF":5.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491940","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 : 2025-02-21DOI: 10.1016/j.ijpharm.2025.125380
M.T. Khulood , U.S. Jijith , P.P. Naseef , Sirajudheen M. Kallungal , V.S. Geetha , K. Pramod
Metal-organic frameworks (MOFs) are emerging crystalline porous materials with significant potential in biomedical applications, particularly as drug delivery systems (DDS). MOFs, composed of metal ions or clusters linked by organic ligands, feature large surface areas, adjustable pores, and diverse functionalities. This review comprehensively examines MOFs as advanced DDS, detailing their structures, synthesis, and drug loading mechanisms. We highlight high drug loading capacity and controlled release capabilities of MOF. Developments of design strategies for MOF-based DDS, namely, surface functionalization for targeted delivery and stimuli-responsive MOFs for controlled release, have been discussed and explored. The use of MOFs for delivering therapeutic agents such as small molecules, peptides, proteins, nucleic acids, and cancer drugs is discussed. Challenges addressed include stability, degradation in biological environments, potential toxicity, and scalability. Advances in hybrid MOF-based DDS, integrating MOFs with polymers, lipids, or nanoparticles for improved delivery, are also examined.
{"title":"Advances in metal-organic framework-based drug delivery systems","authors":"M.T. Khulood , U.S. Jijith , P.P. Naseef , Sirajudheen M. Kallungal , V.S. Geetha , K. Pramod","doi":"10.1016/j.ijpharm.2025.125380","DOIUrl":"10.1016/j.ijpharm.2025.125380","url":null,"abstract":"<div><div>Metal-organic frameworks (MOFs) are emerging crystalline porous materials with significant potential in biomedical applications, particularly as drug delivery systems (DDS). MOFs, composed of metal ions or clusters linked by organic ligands, feature large surface areas, adjustable pores, and diverse functionalities. This review comprehensively examines MOFs as advanced DDS, detailing their structures, synthesis, and drug loading mechanisms. We highlight high drug loading capacity and controlled release capabilities of MOF. Developments of design strategies for MOF-based DDS, namely, surface functionalization for targeted delivery and stimuli-responsive MOFs for controlled release, have been discussed and explored. The use of MOFs for delivering therapeutic agents such as small molecules, peptides, proteins, nucleic acids, and cancer drugs is discussed. Challenges addressed include stability, degradation in biological environments, potential toxicity, and scalability. Advances in hybrid MOF-based DDS, integrating MOFs with polymers, lipids, or nanoparticles for improved delivery, are also examined.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125380"},"PeriodicalIF":5.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483114","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 : 2025-02-21DOI: 10.1016/j.ijpharm.2025.125382
Yaseen Hussain , Ben-Gang You , Linyu Huang , Xiaoyin Liu , Amos Dormocara , Kiramat Ali Shah , Tariq Ali , Qing-Ri Cao , Beom-Jin Lee , Serag Eldin I. Elbehairi , Haroon Iqbal , Jing-Hao Cui
Skin cancer is one among the common types of cancers, affecting millions of individual globally. The conventional anticancer therapy such as chemotherapy results in worst systemic and local side effects as well as inhibit the growth of healthy cells around the tumor cells. Dissolving microneedles (DMNs) is a groundbreaking technology with less invasive and more targeted features. Physically, these tiny dissolving needles deliver the anticancer payloads drug to the tumor site after its direct application on the skin surface. Specifically, the DMNs release the anticancer drug cargoes into the cancerous cell sparing the healthy cells around the tumor, thus has provided a significant contribution in the landscape of traditional skin cancer therapy. This targeted therapeutic approach of dissolving microneedles shows a significant therapeutic outcome in decreasing the growth of cancer cells in pre-clinical studies. Dissolving microneedles (DMNs) have demonstrated effectiveness in the targeted delivery of drugs, genes, and vaccines specifically at the site of skin tumors. This method mimics the localized release of adjuvants and immunomodulators, leading to significant humoral and cellular immune responses that are beneficial for skin cancer therapy. In this review, the current trends and potential roles of dissolving microneedles in delivering therapeutic agents focused on treating skin melanoma have been highlighted, drawing insights from recent literature. This emphasizes the promising applications of DMNs in enhancing treatment outcomes for skin cancer patients. Lastly, future perspectives were identified for improving the therapeutic potential and translation of DMNs into clinic.
{"title":"Dissolving microneedles for melanoma: Most recent updates, challenges, and future perspectives","authors":"Yaseen Hussain , Ben-Gang You , Linyu Huang , Xiaoyin Liu , Amos Dormocara , Kiramat Ali Shah , Tariq Ali , Qing-Ri Cao , Beom-Jin Lee , Serag Eldin I. Elbehairi , Haroon Iqbal , Jing-Hao Cui","doi":"10.1016/j.ijpharm.2025.125382","DOIUrl":"10.1016/j.ijpharm.2025.125382","url":null,"abstract":"<div><div>Skin cancer is one among the common types of cancers, affecting millions of individual globally. The conventional anticancer therapy such as chemotherapy results in worst systemic and local side effects as well as inhibit the growth of healthy cells around the tumor cells. Dissolving microneedles (DMNs) is a groundbreaking technology with less invasive and more targeted features. Physically, these tiny dissolving needles deliver the anticancer payloads drug to the tumor site after its direct application on the skin surface. Specifically, the DMNs release the anticancer drug cargoes into the cancerous cell sparing the healthy cells around the tumor, thus has provided a significant contribution in the landscape of traditional skin cancer therapy. This targeted therapeutic approach of dissolving microneedles shows a significant therapeutic outcome in decreasing the growth of cancer cells in pre-clinical studies. Dissolving microneedles (DMNs) have demonstrated effectiveness in the targeted delivery of drugs, genes, and vaccines specifically at the site of skin tumors. This method mimics the localized release of adjuvants and immunomodulators, leading to significant humoral and cellular immune responses that are beneficial for skin cancer therapy. In this review, the current trends and potential roles of dissolving microneedles in delivering therapeutic agents focused on treating skin melanoma have been highlighted, drawing insights from recent literature. This emphasizes the promising applications of DMNs in enhancing treatment outcomes for skin cancer patients. Lastly, future perspectives were identified for improving the therapeutic potential and translation of DMNs into clinic.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125382"},"PeriodicalIF":5.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483115","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 : 2025-02-21DOI: 10.1016/j.ijpharm.2025.125381
Vahid Rahimkhoei , Ali Akbari , Amar Yasser Jassim , Uday Abdul-Reda Hussein , Masoud Salavati-Niasari
Cancer stem cells (CSCs) are a special group of cells that start, regenerate, and maintain the growth of tumors. Cancer stem cells (CSCs) contribute to the dissemination of tumors, their recurrence following treatment, and the mechanisms by which cancers develop resistance to therapies. CSCs reside in a unique microenvironment influenced by a variety of factors from their immediate surroundings. These factors include low oxygen levels, too much new blood vessel growth, a shift in how cells use energy from breathing oxygen to breaking down glucose, and an increase in certain markers and signals related to stem cells that help remove drugs from the body. Antibodies and special molecules that focus on the unique features keeping the environment stable are used to deliver cancer treatments to CSCs. As a result, nanoparticles are extremely effective in delivering drugs that combat cancer directly to cancer stem cells. Right now, stem cell nanotechnology is a new and interesting area of study. Some experiments on how stem cells interact with tiny structures or materials have shown good results. The importance of tiny structures and materials in creating treatments using stem cells for diseases and injuries has been clearly understood. The way nanomaterials are built and their characteristics influence how stem cells grow and change. This area of study is a new and exciting field where material science meets medicine. This review talks about the biology of CSCs and new ways to create nanoparticles (NPs) that can deliver cancer drugs specifically to these CSCs. This review talks about the creation of different types of tiny particles, including synthetic and natural polymer particles, lipid particles, inorganic particles, protein particles that can assemble themselves, combined antibody-drug particles, and small bubbles called nanovesicles, all aimed at targeting cancer stem cells. This paper talks about recent progress and opinions on using nanotechnology in stem cell research and therapy. It also covers how nanoparticles can help track, control, and improve the retention of stem cells.
{"title":"Recent advances in targeting cancer stem cells by using nanomaterials","authors":"Vahid Rahimkhoei , Ali Akbari , Amar Yasser Jassim , Uday Abdul-Reda Hussein , Masoud Salavati-Niasari","doi":"10.1016/j.ijpharm.2025.125381","DOIUrl":"10.1016/j.ijpharm.2025.125381","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are a special group of cells that start, regenerate, and maintain the growth of tumors. Cancer stem cells (CSCs) contribute to the dissemination of tumors, their recurrence following treatment, and the mechanisms by which cancers develop resistance to therapies. CSCs reside in a unique microenvironment influenced by a variety of factors from their immediate surroundings. These factors include low oxygen levels, too much new blood vessel growth, a shift in how cells use energy from breathing oxygen to breaking down glucose, and an increase in certain markers and signals related to stem cells that help remove drugs from the body. Antibodies and special molecules that focus on the unique features keeping the environment stable are used to deliver cancer treatments to CSCs. As a result, nanoparticles are extremely effective in delivering drugs that combat cancer directly to cancer stem cells. Right now, stem cell nanotechnology is a new and interesting area of study. Some experiments on how stem cells interact with tiny structures or materials have shown good results. The importance of tiny structures and materials in creating treatments using stem cells for diseases and injuries has been clearly understood. The way nanomaterials are built and their characteristics influence how stem cells grow and change. This area of study is a new and exciting field where material science meets medicine. This review talks about the biology of CSCs and new ways to create nanoparticles (NPs) that can deliver cancer drugs specifically to these CSCs. This review talks about the creation of different types of tiny particles, including synthetic and natural polymer particles, lipid particles, inorganic particles, protein particles that can assemble themselves, combined antibody-drug particles, and small bubbles called nanovesicles, all aimed at targeting cancer stem cells. This paper talks about recent progress and opinions on using nanotechnology in stem cell research and therapy. It also covers how nanoparticles can help track, control, and improve the retention of stem cells.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125381"},"PeriodicalIF":5.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478576","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 : 2025-02-20DOI: 10.1016/j.ijpharm.2025.125384
Giada Diana , Andrea Milanesi , Alessandro Candiani , Alessandro Sodano , Paolo Rassè , Andrea Foglio Bonda , Laura Alessandroni , Lorella Giovannelli , Lorena Segale , Jean Daniel Coïsson
Spray drying is a practical solution to convert oil-in-water emulsion into solid microparticles. In this work, a formulation study was conducted to identify the best composition of vitamin D3-loaded oil-in-water emulsion to process via a lab-scale spray dryer. The emulsion was composed of vitamin D3 oily solution (7 % w/w) and maltodextrin (21 % w/w), arabic gum (9 % w/w) and pea protein hydrolysate (1 % w/w) aqueous solution and was characterized by optimal stability (> 24 h). The spray drying process (Tin: 160 °C; Tout: 94 °C; Gas atomization: 1.75 bar; Feeding rate: 8.75 g/min) was successful: the process yield was good, and the obtained powder had an acceptable residual humidity. The average diameter of microparticles was 23 µm with a quite wide particle size distribution. The oil and vitamin D3 recovered from the powder were 85.69 ± 3.91 % and 80.10 ± 9.94 % of the expected, respectively. The accelerated stability and photostability study results showed that the percentage of vitamin D3 present in the powder after storage was twice compared to vitamin D3 in oil solution stored at the same conditions. Moreover, the scale-up of the process from lab- to pilot-scale spray dryer was encouraging. Regardless of the top or bottom spray set-up, the pilot scale treatments increased the production rate and improved drying efficiency. The top spray configuration and a low inlet temperature guaranteed a yield of over 86 %, about 3 % residual humidity in the powder, and preserved the oil quality, maintaining a peroxide value comparable to the initial one.
{"title":"Spray drying of an oil-in-water emulsion containing vitamin D3: a synergy between formulation and process conditions to obtain microparticles","authors":"Giada Diana , Andrea Milanesi , Alessandro Candiani , Alessandro Sodano , Paolo Rassè , Andrea Foglio Bonda , Laura Alessandroni , Lorella Giovannelli , Lorena Segale , Jean Daniel Coïsson","doi":"10.1016/j.ijpharm.2025.125384","DOIUrl":"10.1016/j.ijpharm.2025.125384","url":null,"abstract":"<div><div>Spray drying is a practical solution to convert oil-in-water emulsion into solid microparticles. In this work, a formulation study was conducted to identify the best composition of vitamin D3-loaded oil-in-water emulsion to process via a lab-scale spray dryer. The emulsion was composed of vitamin D3 oily solution (7 % w/w) and maltodextrin (21 % w/w), arabic gum (9 % w/w) and pea protein hydrolysate (1 % w/w) aqueous solution and was characterized by optimal stability (> 24 h). The spray drying process (T<sub>in</sub>: 160 °C; T<sub>out</sub>: 94 °C; Gas atomization: 1.75 bar; Feeding rate: 8.75 g/min) was successful: the process yield was good, and the obtained powder had an acceptable residual humidity. The average diameter of microparticles was 23 µm with a quite wide particle size distribution. The oil and vitamin D3 recovered from the powder were 85.69 ± 3.91 % and 80.10 ± 9.94 % of the expected, respectively. The accelerated stability and photostability study results showed that the percentage of vitamin D3 present in the powder after storage was twice compared to vitamin D3 in oil solution stored at the same conditions. Moreover, the scale-up of the process from lab- to pilot-scale spray dryer was encouraging. Regardless of the top or bottom spray set-up, the pilot scale treatments increased the production rate and improved drying efficiency. The top spray configuration and a low inlet temperature guaranteed a yield of over 86 %, about 3 % residual humidity in the powder, and preserved the oil quality, maintaining a peroxide value comparable to the initial one.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125384"},"PeriodicalIF":5.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476615","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}
Degenerative ocular diseases such as age-related macular degeneration (AMD) are typically treated with intravitreal (IVT) injections of anti-VEGF antibodies such as bevacizumab (BVZ). However, frequent IVT injections are associated with significant risks, including adverse effects and low patient compliance. This paper proposes solid lipid nanoparticles (SLNs) as an innovative drug delivery system to address these challenges. Indeed, SLNs offer advantages such as improved stability and prolonged release of the loaded compounds. After assessing BVZ prolonged release from SLNs by in vitro release studies, accurate in vivo studies were performed in a laser-induced CNV model in Brown Norway rats. The aim was to evaluate the efficacy of BVZ-SLNs in comparison to conventional treatments like Avastin®. Techniques including optical coherence tomography (OCT) were employed to assess the potential neovascularization inhibition. The results show that BVZ-SLNs administration can significantly decrease vascular density, even with a difference of 3.7% with Avastin®. Overall, the findings underscore SLNs as a promising platform for ocular drug delivery offering a valid strategy for enhanced therapeutic efficacy and patient compliance in the treatment of degenerative ocular pathologies.
{"title":"A novel bevacizumab delivery system using solid lipid nanoparticles for potential wet age-related macular degeneration treatment: An in vivo study","authors":"Ángel Parra-Sánchez , Gema Martínez-Navarrete , Giulia Accomasso , Giulia Chindamo , Daniela Chirio , Elena Peira , Simona Sapino , Adela Bernabeu-Zornoza , Alejandro Gombau-García , Marina Gallarate , Eduardo Fernández","doi":"10.1016/j.ijpharm.2025.125379","DOIUrl":"10.1016/j.ijpharm.2025.125379","url":null,"abstract":"<div><div>Degenerative ocular diseases such as age-related macular degeneration (AMD) are typically treated with intravitreal (IVT) injections of anti-VEGF antibodies such as bevacizumab (BVZ). However, frequent IVT injections are associated with significant risks, including adverse effects and low patient compliance. This paper proposes solid lipid nanoparticles (SLNs) as an innovative drug delivery system to address these challenges. Indeed, SLNs offer advantages such as improved stability and prolonged release of the loaded compounds. After assessing BVZ prolonged release from SLNs by <em>in vitro</em> release studies, accurate <em>in vivo</em> studies were performed in a laser-induced CNV model in Brown Norway rats. The aim was to evaluate the efficacy of BVZ-SLNs in comparison to conventional treatments like Avastin®. Techniques including optical coherence tomography (OCT) were employed to assess the potential neovascularization inhibition. The results show that BVZ-SLNs administration can significantly decrease vascular density, even with a difference of 3.7% with Avastin®. Overall, the findings underscore SLNs as a promising platform for ocular drug delivery offering a valid strategy for enhanced therapeutic efficacy and patient compliance in the treatment of degenerative ocular pathologies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125379"},"PeriodicalIF":5.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471340","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}
Previous studies showed that intradermal delivery of naked plasmid DNA using the needle-free pyro-drive jet injector, Actranza™, significantly enhanced gene expression compared to needle-syringe injections in animals. Here, we targeted intra-articular (IA) tissues, including cartilage in the rat knee joint. In order to accurately deliver the DNA solution to the joint cavity, the Actranza prototype attaching a 30G needle as a guide was used (30G-Acranza). The injection powers are controllable adjusting the amounts of ignition powder (IP) and smokeless powder (SP). Preliminary tests determined an optimal injection site (5 mm depth from the skin surface into the anterior joint cavity with the knee flexed) and injection volume (30 µL). Initial trials with 30G-Actranza-25/40 (IP/SP = 25 mg/40 mg) showed luciferase plasmid (pLuc) expression levels (relative luminescence units, RLU) that were approximately 40 times higher than manual syringe injections 24 h after the administration. Additional Green Fluorescent Protein plasmid (pGFP) experiments detected fluorescence in chondrocytes and cruciate ligament fibroblasts. The higher-powered 30G-Actranza-35/40 further increased pLuc expression compared to syringe injections (∼ 100 times). The expression remained detectable 10 days post-injection, though reduced from day one. Speed-controlled tests indicated that pLuc expression levels increased with injection speed, reaching saturation at 693 µL/s of 30G-Actranza-35/40. Reference data showed transdermal needle-free jet injection favored skin and proximal tissues over IA sites. In conclusion, needle-equipped jet injection effectively transfects naked plasmid DNA into IA tissues like cartilage, synovium, ligaments, and tendons with potential applications for encapsulated tissues such as tumors, broadening prospects for gene therapy, gene editing, and regenerative medicine.
{"title":"Intra-articular administration of naked plasmid DNA with a guide-equipe jet injector in rat knee joints","authors":"Kazuhiro Terai , Ryusho Kariya , Hiromi Ogata-Aoki , Seiji Okada","doi":"10.1016/j.ijpharm.2025.125374","DOIUrl":"10.1016/j.ijpharm.2025.125374","url":null,"abstract":"<div><div>Previous studies showed that intradermal delivery of naked plasmid DNA using the needle-free pyro-drive jet injector, Actranza™, significantly enhanced gene expression compared to needle-syringe injections in animals. Here, we targeted intra-articular (IA) tissues, including cartilage in the rat knee joint. In order to accurately deliver the DNA solution to the joint cavity, the Actranza prototype attaching a 30G needle as a guide was used (30G-Acranza). The injection powers are controllable adjusting the amounts of ignition powder (IP) and smokeless powder (SP). Preliminary tests determined an optimal injection site (5 mm depth from the skin surface into the anterior joint cavity with the knee flexed) and injection volume (30 µL). Initial trials with 30G-Actranza-25/40 (IP/SP = 25 mg/40 mg) showed luciferase plasmid (pLuc) expression levels (relative luminescence units, RLU) that were approximately 40 times higher than manual syringe injections 24 h after the administration. Additional Green Fluorescent Protein plasmid (pGFP) experiments detected fluorescence in chondrocytes and cruciate ligament fibroblasts. The higher-powered 30G-Actranza-35/40 further increased pLuc expression compared to syringe injections (∼ 100 times). The expression remained detectable 10 days post-injection, though reduced from day one. Speed-controlled tests indicated that pLuc expression levels increased with injection speed, reaching saturation at 693 µL/s of 30G-Actranza-35/40. Reference data showed transdermal needle-free jet injection favored skin and proximal tissues over IA sites. In conclusion, needle-equipped jet injection effectively transfects naked plasmid DNA into IA tissues like cartilage, synovium, ligaments, and tendons with potential applications for encapsulated tissues such as tumors, broadening prospects for gene therapy, gene editing, and regenerative medicine.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125374"},"PeriodicalIF":5.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467935","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}
Ultrafine bubbles (UFBs), which have a diameter < 1 μm, are renowned for their stability in liquid because of the effects of Brownian motion. The unique physicochemical properties and diverse biological effects of UFBs have potential industrial and biological applications. One important property of UFBs is their negative surface charge, which is thought to be able to influence the positively charged intestinal enzymatic activity and to increase peptide drug mucosal absorption. In this study, insulin was used as the peptide drug model and administered to rats both intestinally and orally at different concentrations of UFB solution to examine the effects of UFBs on the mucosal absorption of insulin. The UFB solution promoted mucosal insulin absorption. Increasing the number of UFBs in solution increased both ileal and oral insulin absorption. To identify the mechanism responsible for this increased insulin absorption, we examined insulin degradation in pepsin and trypsin solutions and found that the presence of UFBs slowed insulin degradation. The biological safety of UFBs in water was evaluated to examine their potential future health applications. UFBs did not affect common blood biochemical parameters or the health of organs and mucosal membranes. To our knowledge, this is the first study to provide evidence for the effects of UFBs in water on oral insulin absorption. In conclusion, the use of UFBs in water represents a novel method for increasing the oral absorption of peptide drugs, such as insulin. UFBs may be promising candidates as a delivery tool for clinical drug development.
{"title":"Boosting the oral absorption of insulin using Ultrafine bubbles","authors":"Risako Morishita , Mayuko Hirosoko , Miwa Toyonaga , Hayato Yoshida , Yuuya Takaguchi , Akikatsu Yanagawa , Ryosuke Murase , Ai Yoshida , Yoshiharu Kasahara , Ikumi Kajiwara , Shin Shimizu , Noriyasu Kamei , Mariko Takeda-Morishita","doi":"10.1016/j.ijpharm.2025.125378","DOIUrl":"10.1016/j.ijpharm.2025.125378","url":null,"abstract":"<div><div>Ultrafine bubbles (UFBs), which have a diameter < 1 μm, are renowned for their stability in liquid because of the effects of Brownian motion. The unique physicochemical properties and diverse biological effects of UFBs have potential industrial and biological applications. One important property of UFBs is their negative surface charge, which is thought to be able to influence the positively charged intestinal enzymatic activity and to increase peptide drug mucosal absorption. In this study, insulin was used as the peptide drug model and administered to rats both intestinally and orally at different concentrations of UFB solution to examine the effects of UFBs on the mucosal absorption of insulin. The UFB solution promoted mucosal insulin absorption. Increasing the number of UFBs in solution increased both ileal and oral insulin absorption. To identify the mechanism responsible for this increased insulin absorption, we examined insulin degradation in pepsin and trypsin solutions and found that the presence of UFBs slowed insulin degradation. The biological safety of UFBs in water was evaluated to examine their potential future health applications. UFBs did not affect common blood biochemical parameters or the health of organs and mucosal membranes. To our knowledge, this is the first study to provide evidence for the effects of UFBs in water on oral insulin absorption. In conclusion, the use of UFBs in water represents a novel method for increasing the oral absorption of peptide drugs, such as insulin. UFBs may be promising candidates as a delivery tool for clinical drug development.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"673 ","pages":"Article 125378"},"PeriodicalIF":5.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465542","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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