International Journal of Pharmaceutics最新文献_第3页

Biopolymeric 3D printed scaffolds as a versatile tissue engineering treatment for congenital diaphragmatic hernia

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-02-02 DOI: 10.1016/j.ijpharm.2025.125313

Aikaterini Dedeloudi , Fatima Farzeen , Vlad-Nicolae Lesutan , Robyn Irwin , Matthew P. Wylie , Sune Andersen , Mary Patrice Eastwood , Dimitrios A. Lamprou

Congenital diaphragmatic hernia (CDH) is a rare disease in which neonates are born with pulmonary hypoplasia and a diaphragmatic defect. Survival is improving due to advances in fetal intervention for pulmonary hypoplasia leading to increased use of scaffolds for repair. Scaffolds have a significant morbidity rate with recurrence, small bowel obstruction and infrequently postoperative infections. 3D printing (3DP) is a promising technology for the fabrication of personalized medical devices characterised by a more precise and targeted approach to tissue engineering and drug delivery. In this study, blank thermoplastic polyurethane (TPU) and gentamicin sulfate (GNS)-loaded filaments (1 % and 1.5 %wt.) were fabricated with hot melt extrusion (HME) and subsequently processed through 3DP for scaffold manufacturing. Geometrical attributes of the scaffolds, including a specific % infill, were predefined through computer aided design (CAD) and printing parameters were optimised. Physicochemical analysis involving material compatibility and thermal properties of all formulations were examined, determining their thermal and chemical stability during 3DP. Mechanical analysis showed that polymeric matrixes resemble to diaphragm tissue, exhibiting adequate and reproducible elastic performance, while cell studies confirmed TPU’s supportive capacity for cellular attachment. Additionally, in vitro dissolution and bacterial studies were carried out for up to a week, denoting GNS’s sustained release from the polymeric matrices and efficient bactericidal activity to Gram-positive and Gram-negative bacteria, respectively. Therefore, TPU is a potential biomaterial that can be efficiently used for developing diverse 3D printed diaphragm-like scaffolds possessing antimicrobial activity for CDH.

{"title":"Biopolymeric 3D printed scaffolds as a versatile tissue engineering treatment for congenital diaphragmatic hernia","authors":"Aikaterini Dedeloudi , Fatima Farzeen , Vlad-Nicolae Lesutan , Robyn Irwin , Matthew P. Wylie , Sune Andersen , Mary Patrice Eastwood , Dimitrios A. Lamprou","doi":"10.1016/j.ijpharm.2025.125313","DOIUrl":"10.1016/j.ijpharm.2025.125313","url":null,"abstract":"<div><div>Congenital diaphragmatic hernia (CDH) is a rare disease in which neonates are born with pulmonary hypoplasia and a diaphragmatic defect. Survival is improving due to advances in fetal intervention for pulmonary hypoplasia leading to increased use of scaffolds for repair. Scaffolds have a significant morbidity rate with recurrence, small bowel obstruction and infrequently postoperative infections. 3D printing (3DP) is a promising technology for the fabrication of personalized medical devices characterised by a more precise and targeted approach to tissue engineering and drug delivery. In this study, blank thermoplastic polyurethane (TPU) and gentamicin sulfate (GNS)-loaded filaments (1 % and 1.5 %wt.) were fabricated with hot melt extrusion (HME) and subsequently processed through 3DP for scaffold manufacturing. Geometrical attributes of the scaffolds, including a specific % infill, were predefined through computer aided design (CAD) and printing parameters were optimised. Physicochemical analysis involving material compatibility and thermal properties of all formulations were examined, determining their thermal and chemical stability during 3DP. Mechanical analysis showed that polymeric matrixes resemble to diaphragm tissue, exhibiting adequate and reproducible elastic performance, while cell studies confirmed TPU’s supportive capacity for cellular attachment. Additionally, <em>in vitro</em> dissolution and bacterial studies were carried out for up to a week, denoting GNS’s sustained release from the polymeric matrices and efficient bactericidal activity to Gram-positive and Gram-negative bacteria, respectively. Therefore, TPU is a potential biomaterial that can be efficiently used for developing diverse 3D printed diaphragm-like scaffolds possessing antimicrobial activity for CDH.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"672 ","pages":"Article 125313"},"PeriodicalIF":5.3,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143140959","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}

引用次数: 0

Microbubble-encapsulation of actives for controlled release and its application to the taste-masking of acetaminophen

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-02-02 DOI: 10.1016/j.ijpharm.2025.125309

Albert T. Poortinga , Cornelus F. van Nostrum

In this work we present a new encapsulation method that allows for the controlled release of drugs under simulated small intestinal conditions. This method consists of encapsulation within microbubbles and is characterized by an unprecedented combination of excellent barrier properties and fast and complete triggered release. The method was applied to produce a drink containing taste-masked acetaminophen as a model drug. Micronized acetaminophen (paracetamol) was dispersed in cyclohexane containing pharma-approved hydrophobized silica particles and the resulting dispersion was emulsified in an aqueous phase containing dispersed hydrophobized silica particles and dissolved maltodextrin. The resulting solid-in-oil-in-water emulsion was washed to remove unencapsulated acetaminophen and subsequently freeze-dried to remove both the water and the cyclohexane. This produced a dry material that after reconstitution in water created a suspension of microbubbles containing acetaminophen particles, i.e. a solid-in-gas-in-water dispersion. The encapsulation efficiency was well over 90% and hardly any acetaminophen escaped from the microbubbles during storage for 24 h in aqueous solution. Also, encapsulates were stable in the presence of saliva as well as during in vitro incubation with stomach juice. In line with this, sensory tests showed an excellent masking of the taste of the drug. In vitro incubation with simulated intestinal fluid containing bile salts triggered fast and near complete release of the encapsulated acetaminophen, which should assure good bioavailability in vivo. The described encapsulates that are stable for at least days, are thus expected to be suitable for taste-masking or enteric release applications in liquid formulations, including foods.

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引用次数: 0

Overview on LNP-mRNA encapsulation unit operation: Mixing technologies, scalability, and influence of formulation & process parameters on physico-chemical characteristics

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-02-01 DOI: 10.1016/j.ijpharm.2025.125297

Laurine Hourdel , Noureddine Lebaz , Florent Peral , Manon Ripoll , Stéphanie Briançon , Fethi Bensaid , Sumit Luthra , Claudia Cogné

Nanoparticles carrying active drug substances have been used since the 70′s and have undergone numerous improvements since then. Nowadays, the latest generation of nanoparticles, called lipid nanoparticles (LNPs), is used for different applications such as vaccines and cancer treatments and offer a versatile approach to delivering genetic materials like RNA. LNPs are non-viral delivery vehicles obtained by the self-assembly of lipids during the rapid mixing of an aqueous phase containing mRNA with an organic phase containing lipids. During this process, mRNA is encapsulated within the LNP due to electrostatic interaction with an ionizable lipid. Different methods to produce LNPs are described in the literature and, as of now, continuous methods are mostly used to produce LNP-encapsulated mRNA (LNP-mRNA). T-shaped mixers are commonly used to produce mRNA-LNPs. This technology can operate at two different scales: microfluidic chips which can range from tens to hundreds of microns in size, and millimetric tubing for production scale up. This review intends to describe LNP-mRNA characteristics and their production modes with a special focus on the challenges related to the mixing quality, especially during scale-up.

{"title":"Overview on LNP-mRNA encapsulation unit operation: Mixing technologies, scalability, and influence of formulation & process parameters on physico-chemical characteristics","authors":"Laurine Hourdel , Noureddine Lebaz , Florent Peral , Manon Ripoll , Stéphanie Briançon , Fethi Bensaid , Sumit Luthra , Claudia Cogné","doi":"10.1016/j.ijpharm.2025.125297","DOIUrl":"10.1016/j.ijpharm.2025.125297","url":null,"abstract":"<div><div>Nanoparticles carrying active drug substances have been used since the 70′s and have undergone numerous improvements since then. Nowadays, the latest generation of nanoparticles, called lipid nanoparticles (LNPs), is used for different applications such as vaccines and cancer treatments and offer a versatile approach to delivering genetic materials like RNA. LNPs are non-viral delivery vehicles obtained by the self-assembly of lipids during the rapid mixing of an aqueous phase containing mRNA with an organic phase containing lipids. During this process, mRNA is encapsulated within the LNP due to electrostatic interaction with an ionizable lipid. Different methods to produce LNPs are described in the literature and, as of now, continuous methods are mostly used to produce LNP-encapsulated mRNA (LNP-mRNA). T-shaped mixers are commonly used to produce mRNA-LNPs. This technology can operate at two different scales: microfluidic chips which can range from tens to hundreds of microns in size, and millimetric tubing for production scale up. This review intends to describe LNP-mRNA characteristics and their production modes with a special focus on the challenges related to the mixing quality, especially during scale-up.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"672 ","pages":"Article 125297"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122823","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}

引用次数: 0

Design and characterization of κ-Carrageenan:PVA hydrogels to repurpose the topical delivery of betamethasone

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-02-01 DOI: 10.1016/j.ijpharm.2025.125305

Ana Isabel Barbosa , Ibraheem Yousef , Sofia A. Costa Lima , Salette Reis

Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, and despite the several existing treatments, it is necessary to find new alternative topical therapies. Hydrogels may represent a good tool to treat AD due to their high water content, making them excellent candidates for drug delivery vehicles in skin research. This work aimed to develop and characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan and polyvinyl alcohol) for cutaneous delivery of betamethasone (up to 0.2 mg mL⁻¹) widely used to manage AD, with high skin retention. Bergamot oil and menthol essential oils were also incorporated into the hydrogels to study their effects on penetration and retention of the corticosteroid. Rheological properties revealed the pseudoplastic behavior of the hydrogels, a favorable characteristic for skin application. Cytocompatibility towards fibroblasts and keratinocytes was determined, revealing safe usage of the hydrogel blends up to 100 mg mL⁻¹, corresponding to 20 µg mL⁻¹ in betamethasone, but was compromised by the presence of the essential oils in the higher hydrogel tested concentrations (50 and 100 mg mL⁻¹). The ex vivo pig ear skin permeation assay showed that hydrogels promote betamethasone retention up to 20 % of the added dose (c.a. 10 µg) even after 24 h of permeation, independently of the use of essential oils’ use in the composition, showing that they might be a good strategy to treat AD skin.

{"title":"Design and characterization of κ-Carrageenan:PVA hydrogels to repurpose the topical delivery of betamethasone","authors":"Ana Isabel Barbosa , Ibraheem Yousef , Sofia A. Costa Lima , Salette Reis","doi":"10.1016/j.ijpharm.2025.125305","DOIUrl":"10.1016/j.ijpharm.2025.125305","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, and despite the several existing treatments, it is necessary to find new alternative topical therapies. Hydrogels may represent a good tool to treat AD due to their high water content, making them excellent candidates for drug delivery vehicles in skin research. This work aimed to develop and characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan and polyvinyl alcohol) for cutaneous delivery of betamethasone (up to 0.2 mg mL<sup>−1</sup>) widely used to manage AD, with high skin retention. Bergamot oil and menthol essential oils were also incorporated into the hydrogels to study their effects on penetration and retention of the corticosteroid. Rheological properties revealed the pseudoplastic behavior of the hydrogels, a favorable characteristic for skin application. Cytocompatibility towards fibroblasts and keratinocytes was determined, revealing safe usage of the hydrogel blends up to 100 mg mL<sup>−1</sup>, corresponding to 20 µg mL<sup>−1</sup> in betamethasone, but was compromised by the presence of the essential oils in the higher hydrogel tested concentrations (50 and 100 mg mL<sup>−1</sup>). The <em>ex vivo</em> pig ear skin permeation assay showed that hydrogels promote betamethasone retention up to 20 % of the added dose (c.a. 10 µg) even after 24 h of permeation, independently of the use of essential oils’ use in the composition, showing that they might be a good strategy to treat AD skin.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"671 ","pages":"Article 125305"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079794","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}

引用次数: 0

One-step engineered mesenchymal stem cell-derived exosomes against hepatic ischemia–reperfusion injury

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125292

Xinfeng Lu , Haitao Hu , Yujie Zhou , Hui Zhang , Chang Xie , Yiyang Sun , Zile Shao , Lin Tang , Yuhao Ren , Jun Chen , Xiao Xu , Nasha Qiu , Haijun Guo

Hepatic ischemia–reperfusion injury (IRI) is an important factor affecting the prognosis of patients undergoing surgery. Exosomes derived from mesenchymal stem cells (MSC-EXOs) are widely used and play a therapeutic role in hepatic IRI. However, natural exosomes lack liver-targeting ability and have low bioavailability. In this study, MSC-EXOs were simply modified with OPDEA-PCL or liver-targeting DSPE-PEG₂₀₀₀-Galactose, forming OPDEA-PCL-modified MSC-EXOs (OP-EXOs) or DSPE-PEG₂₀₀₀-Galactose-modified MSC-EXOs (GPEG-EXOs). In mouse hepatic IRI model, OP-EXOs and GPEG-EXOs both significantly reduced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels in serum after hepatic IRI, alleviating liver injury. Transcriptomic and proteomic analyses showed that OP-EXOs and GPEG-EXOs reduced hepatic IRI by downregulating the expression of S100A8, S100A9, SELP, and ANXA2 in the liver following IRI. This study opens a new paradigm for the treatment of hepatic IRI using engineered MSC-EXOs with the potential to improve the prognosis of liver surgery.

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引用次数: 0

Topical drug formulation for enhanced permeation: A comparison of Bayesian optimisation and response surface methodology with an ibuprofen-loaded poloxamer 407-based formulations case study

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125306

Yongrui Xiao , Tanja Ilić , Anđela Tošić , Branka Ivković , Dimitrios Tsaoulidis , Snežana Savić , Tao Chen

Topical skin products aim to address aesthetic, protective, and/or therapeutic needs through interaction with the human epidermal system. Traditionally, formulation development relies on empirical knowledge and trial-and-error experiments. In this paper, we introduced the Bayesian optimisation method and compared it with the traditional response surface methodology (RSM) for topical drug formulation. The objective was to optimise the formulation composition of ibuprofen gel-like to achieve a maximum flux through in vitro permeation tests (IVPTs). As a model system, poloxamer 407, ethanol, and propylene glycol (PG) were selected as the key excipients, whose concentrations were optimised. Strat-M membrane, serving as a surrogate for human skin, and Franz cell diffusion were employed in IVPTs. Two sets of experiments were conducted under identical conditions for 30 h. Under the RSM approach, the optimised ibuprofen gel-like formulation was identified with a poloxamer 407: ethanol: PG ratio of 20:20:10, achieving a measured permeation flux of 11.28 ± 0.35 μg cm⁻²h⁻¹. In comparison, Bayesian optimisation, after four iterations, yielded an optimised formulation with a ratio of 20.95:19.44:12.14, resulting in a permeation flux of 14.15 ± 0.77 μg cm⁻²h⁻¹. These findings highlight the potential of Bayesian optimisation as an effective tool for improving topical drug formulations.

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引用次数: 0

Quercetin-loaded solid lipid nanoparticles for enhanced anti-helminthic activity

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125308

Sunidhi Sharma , Ruchika Thukral , Lachhman Das Singla , Neena Singla , Diptiman Choudhury

Quercetin, a naturally occurring flavonoid, exhibits various anti-carcinogenic, anti-viral, anti-inflammatory properties, and anti-helminthic properties. Still, a major portion of orally administered quercetin is metabolized in the intestine and only little amount get absorbed in the portal veins, attributing to its poor bioavailability. The lipid content of food increases the solubility, which inspired us to fabricate lipid-based nanoparticles that will be biocompatible, orally administrable, and enhance the effectiveness of quercetin in hosts. Quercetin-loaded solid lipid nanoparticles (SLN-Qt) are spherical-shaped, water-soluble in nature, and nanocarriers having a hydrodynamic size of 130.7 ± 42.0 nm showing a drug entrapment efficiency of 79.75 % with sustained drug release of 37.5 ± 1.5 % within the first 24 h at pH 6.4. The drug release was observed till 6 days with 93.7 ± 3.0 % of drug release at pH 7.4. These results suggest improved drug entrapment, high saturation solubility, and better drug distribution. The in-vivo analysis was performed in house rats (Rattus rattus), which were found infected with Syphacia muris, Aspicularis tetraptera, Hymenolepis diminuta, Hymenolepis nana, Cysticercus fasciolaris, Calodium hepaticum, and/ or Trichuris muris. SLN-Qt (200 mg/Kg) treatment showed a significant reduction of parasite egg counts (85.09 ± 15.00 %) of gastrointestinal helminths after 3-dose weekly treatment. Liver histology and biochemical analysis of blood plasma and liver homogenate showed no toxic effects of quercetin and SLN-Qt. Therefore, SLN-Qt presents a promising strategy for delivering poorly soluble drugs and could be a valuable tool in controlling parasitic infections and diseases.

{"title":"Quercetin-loaded solid lipid nanoparticles for enhanced anti-helminthic activity","authors":"Sunidhi Sharma , Ruchika Thukral , Lachhman Das Singla , Neena Singla , Diptiman Choudhury","doi":"10.1016/j.ijpharm.2025.125308","DOIUrl":"10.1016/j.ijpharm.2025.125308","url":null,"abstract":"<div><div>Quercetin, a naturally occurring flavonoid, exhibits various anti-carcinogenic, anti-viral, anti-inflammatory properties, and anti-helminthic properties. Still, a major portion of orally administered quercetin is metabolized in the intestine and only little amount get absorbed in the portal veins, attributing to its poor bioavailability. The lipid content of food increases the solubility, which inspired us to fabricate lipid-based nanoparticles that will be biocompatible, orally administrable, and enhance the effectiveness of quercetin in hosts. Quercetin-loaded solid lipid nanoparticles (SLN-Qt) are spherical-shaped, water-soluble in nature, and nanocarriers having a hydrodynamic size of 130.7 ± 42.0 nm showing a drug entrapment efficiency of 79.75 % with sustained drug release of 37.5 ± 1.5 % within the first 24 h at pH 6.4. The drug release was observed till 6 days with 93.7 ± 3.0 % of drug release at pH 7.4. These results suggest improved drug entrapment, high saturation solubility, and better drug distribution. The <em>in-vivo</em> analysis was performed in house rats (<em>Rattus rattus</em>), which were found infected with <em>Syphacia muris, Aspicularis tetraptera</em>, <em>Hymenolepis diminuta</em>, <em>Hymenolepis nana</em>, <em>Cysticercus fasciolaris</em>, <em>Calodium hepaticum,</em> and/ or <em>Trichuris muris</em>. SLN-Qt (200 mg/Kg) treatment showed a significant reduction of parasite egg counts (85.09 ± 15.00 %) of gastrointestinal helminths after 3-dose weekly treatment. Liver histology and biochemical analysis of blood plasma and liver homogenate showed no toxic effects of quercetin and SLN-Qt. Therefore, SLN-Qt presents a promising strategy for delivering poorly soluble drugs and could be a valuable tool in controlling parasitic infections and diseases.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"672 ","pages":"Article 125308"},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079812","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}

引用次数: 0

Using density changes to monitor blending with magnesium stearate by terahertz time-domain spectroscopy

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125303

Moritz Anuschek , Thea Nilsson , Anne Linnet Skelbæk-Lorenzen , Thomas Kvistgaard Vilhelmsen , J.Axel Zeitler , Jukka Rantanen

Magnesium stearate (MgSt) is among the most common excipients and the most common lubricant in solid oral products. It is primarily added to tablet formulations to ease ejection during tablet compression. While commonly present in low concentrations, the addition of MgSt substantially affects the final tablet properties. Its impact is further not only concentration dependent but also varies with exposure of the formulation to shear, which worst-case results in over-lubrication. The presented study investigated the applicability of terahertz time-domain spectroscopy (THz-TDS) to monitor the shear-induced blend densification of microcrystalline cellulose blended with MgSt over a range of concentrations (0.3, 0.7, and 1.0 %). The effect of shear was investigated by variation of blending times (5 – 20 min) in a diffusion blender. THz-TDS measurements of the powder blends were acquired in transmission by measuring directly through the mixing container. The refractive index at terahertz frequencies was found to be sufficiently sensitive to resolve the densification of the blend with increased blending times. Thus, THz-TDS blend density measurements can be used as a surrogate parameter to evaluate the total shear exposure of a blend. Considerations regarding implementation are discussed. In the context the approach was integrated with the well-described THz-TDS-based tablet porosity analysis into a unified model to monitor and predict the tensile strength. Including the THz-TDS measurement on the blend allowed for a more accurate description of the tensile strength, reducing the root mean squared error by over 40 % (0.33 MPa). The possibility of monitoring the density changes of a blend non-invasively makes THz-TDS a promising process analytical technology approach for controlling the total shear impact on lubricated blends and tablet quality.

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引用次数: 0

Hair follicle targeting via gelatin coated transferosomes loaded with tofacitinib citrate for enhanced treatment of alopecia areata: Clinical evaluation of alopecia areata patients

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125307

Hamss Gabr , Mohammad Abdel-Halim , Basma Mourad , Mai Rady , Samar Mansour

Alopecia areata (AA) is a complex autoimmune disease that has a negative impact on the psychological well-being of patients. AA is associated with T-cells activation and cytokines release leading to collapse of immune privilege of hair follicles (HF). Tofacitinib, a JAK 1&3 inhibitor, exhibited effectiveness in AA treatment. The aim of this study was to develop gelatin-coated transferosomes (GLTS) to deliver tofactinib specifically to the HF to enhance the treatment of AA. GLTS were evaluated for ex vivo skin permeation, localization in skin layers by the tape stripping technique and Confocal microscopy. Finally, GLTS gel was applied topically for the treatment of AA patients, where seven AA patients with recalcitrant lesions (5 males and 2 females) were included in this study, then they were evaluated clinically and dermoscopically to assess the efficacy of treatment. GLTS of size 223.23 ± 16.43 nm, exhibited the highest HF localization by tape stripping (7.8561 ± 0.77 μg), and the highest mean fluorescence intensity in HF (84.63 ± 7.98 rfu). Additionally, hair regrowth in all AA patients was observed after 12 weeks with up to 80 % improvement.

The present work proposed effective formulations for HF targeting of tofacitinib and proved enhanced clinical efficacy in recalcitrant AA patients with positive feedback.

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引用次数: 0

Folate conjugated Nano-Lipid construct of Paclitaxel for site-specific lung squamous carcinoma targeting

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2025-01-31 DOI: 10.1016/j.ijpharm.2025.125312

Vaibhav Rajoriya, Ravikant Gupta, Sudha Vengurlekar, Sachin Kumar Jain

The objective of this study was to evaluate the effectiveness of folate-conjugated nano-lipid constructs (F-NLCs) for targeting lung squamous carcinoma through both ex-vivo and in-vivo studies. Ligand-conjugated (F-NLCs) and non-conjugated (P-NLCs) formulations were prepared using the solvent evaporation method, with paclitaxel as the reference drug. The formulations were characterized for particle size, zeta potential, encapsulation efficiency, and drug loading capacity. The average particle size of P-NLCs and F-NLCs was found to be 190.1 ± 1.9 nm and 231.3 ± 2.3 nm, respectively. The percent entrapment efficiency of P-NLCs and F-NLCs was 85.14 ± 1.4 % and 82.42 ± 1.2 %, respectively. The drug loading for P-NLCs and F-NLCs was 25.3 ± 1.1 % and 24.2 ± 1.3 %, respectively. The haemolytic study revealed lower toxicity for F-NLCs (4.36 ± 0.6 %) compared to P-NLCs (12.36 ± 0.8 %) and paclitaxel (25.41 ± 0.4 %). Ex-vivo studies, employing the SRB method, demonstrated GI50 (µM) values of 9.72 for P-NLCs and 5.84 for F-NLCs, compared to 18.51 for the paclitaxel solution. Cellular uptake studies using Rhodamine-B dye-loaded NLCs (F-D-NLCs), observed through fluorescence microscopy, indicated higher accumulation in the lung sac compared to D-NLCs. In vivo research, focusing on biodistribution and pharmacokinetics, was conducted on Wistar rats to confirm the efficacy of F-NLCs. Biodistribution results showed concentrations of 25.86 ± 0.39 % for F-NLCs and 3.14 ± 0.46 % for the paclitaxel solution in lung squamous carcinoma cells, indicating a significant improvement in drug concentration within carcinogenic squamous cells with F-NLCs. The findings conclude that F-NLCs are a safe, stable, and promising drug delivery system for the targeted treatment of lung squamous carcinoma.

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引用次数: 0