International Journal of Pharmaceutics最新文献

{"title":"Characterization of anatomical variations of the nasal cavity in a subset of European patients and their impact on intranasal drug delivery","authors":"Mike Pasteur ,&nbsp;Guillaume Arsouze ,&nbsp;Guy Ilango ,&nbsp;Déborah Le Pennec ,&nbsp;Dimitri Kulker ,&nbsp;Anaïs Heyraud ,&nbsp;Jean-Philippe Cottier ,&nbsp;Charles Aussedat ,&nbsp;Nathalie Heuzé-Vourc’h ,&nbsp;Virginie Hervé ,&nbsp;Sandrine Le Guellec","doi":"10.1016/j.ijpharm.2024.124851","DOIUrl":"10.1016/j.ijpharm.2024.124851","url":null,"abstract":"<div><div>Anatomical 3D-printed nasal casts are valuable models to investigate intranasal drug deposition, providing preclinical data that cannot be obtained in animal models. However, these models are limited since they are often derived from a single patient or represent a mean of several groups. The present study aimed to better characterize the anatomical differences of the nasal cavity in a European sub-population and to assess the potential impact of anatomical variations on intranasal deposition by medical devices. Ninety-eight cranial computed tomography scans of patients were selected and analyzed in 2D and 3D conformations. They showed symmetry of cavities and a high level of heterogeneity of measurements, especially volume and area, in the population. Three anatomical groups with distinct nasal geometry were identified and 3D nasal casts of the most representative patient of each group were printed. Fluorescein was administered using three medical devices: a nasal spray, a sonic jet nebulizer and a prototype mesh-nebulizer. The deposition profiles were compared with the Aeronose® as a reference. Our results show that anatomical variations influenced the deposition profiles depending on the device, with a higher variation with spray and the mesh-nebulizer. This work emphasises the importance of anatomical parameters on drug intranasal deposition and the need to evaluate inhaled drugs on different 3D nasal casts reflecting the target population.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124851"},"PeriodicalIF":5.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568840","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}

{"title":"RF pulsed plasma modified composite scaffold for enhanced anti-microbial activity and accelerated wound healing","authors":"A.M. Trimukhe ,&nbsp;J.S. Melo ,&nbsp;D. Chaturvedi ,&nbsp;R.D. Jain ,&nbsp;P. Dandekar ,&nbsp;R.R. Deshmukh","doi":"10.1016/j.ijpharm.2024.124864","DOIUrl":"10.1016/j.ijpharm.2024.124864","url":null,"abstract":"<div><div>Infected wounds present significant challenges pertaining to healing and often demand administration of strong antibiotics to patients. Also, drug resistant microbes may alter the physiology of wounds to create biofilms, frequently leading to high morbidity and mortality. In this investigation, a biodegradable, microporous composite agarose-chitosan scaffold was fabricated. Furthermore, its surface was modified with diphenyldiselenide deposition, using low pressure pulsed plasma technology. The optimized plasma parameters, viz. 5_ON/15_OFF (ms) of plasma pulse rate and 80 min of treatment time resulted in scaffolds having enhanced anti-bacterial activity against gram positive microbes like <em>Staphylococcus (S.) aureus</em> and <em>S. epidermidis</em>. The scaffolds were non-toxic to skin cells, as confirmed by the MTT assay. Cell proliferation through plasma treated and untreated scaffolds was assessed by culturing primary human dermal fibroblasts (HdaF) and human keratinocytes (HaCaT) and visualizing via confocal microscopy. Moreover, <em>in-vivo</em> rat model confirmed accelerated wound healing with plasma treated scaffold (100 % on day 14), as compared to the untreated scaffold (100 % on day 16) when compared with over-the-counter (OTC) ointment Betadine (100 % on day 12).</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124864"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500468","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}

{"title":"Effect of conformational landscape on the polymorphism and monomorphism of tizanidine cocrystallization outcomes","authors":"Di Wu ,&nbsp;Lin Fu ,&nbsp;Hongxun Hao ,&nbsp;Chen Chen ,&nbsp;Gang Chen ,&nbsp;Shuyu Li ,&nbsp;Liu Baiqi ,&nbsp;Ting Wang ,&nbsp;Na Wang ,&nbsp;Xin Huang","doi":"10.1016/j.ijpharm.2024.124859","DOIUrl":"10.1016/j.ijpharm.2024.124859","url":null,"abstract":"<div><div>Molecular conformational diversity plays a crucial role in both polymorphic nucleation and cocrystal formation during the cocrystallization process. However, the relationship between molecular conformation and cocrystallization polymorphism is not well-explored. Herein, the impact of molecular conformational landscapes on cocrystallization outcomes was investigated using tizanidine (TZND) as model compound. Four coformers, namely maleic acid (MA), salicylic acid (SA), p-hydroxybenzoic acid (pHBA), and heptanedioic acid (HDA), were employed and five salt forms were developed for the first time. Compared with TZND, all five salts showed significantly improved water solubility and dissolution rate. The cocrystallization behavior of TZND varied with each coformer: MA exhibited solvent-dependent polymorphism, while SA, pHBA, and HDA showed solvent-independent monomorphism. Crystal structure and conformational analyses revealed the conformational variation of TZND across different cocrystallization outcomes. Molecular dynamics simulations and quantum chemical calculations demonstrated that the interplay between solvent effects and coformer interactions determines the dominant conformations of TZND. The cocrystallization nucleation process was also examined, and the molecular mechanism that explains both polymorphism and monomorphism in the cocrystallization of TZND was proposed.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124859"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500462","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}

{"title":"CaCO3-complexed pH-responsive nanoparticles encapsulating mitoxantrone and celastrol enhance tumor chemoimmunotherapy","authors":"Liang Zhang ,&nbsp;Huiqiang Hu ,&nbsp;Wan Cai ,&nbsp;Shungen Chen ,&nbsp;Ping Sheng ,&nbsp;Xiaomei Fu","doi":"10.1016/j.ijpharm.2024.124860","DOIUrl":"10.1016/j.ijpharm.2024.124860","url":null,"abstract":"<div><div>Modulating the immunosuppressive tumor microenvironment (TME) while enhancing antitumor immune responses is a promising strategy. In this study, we designed an acid-sensitive nanosystem (MCCaNPs) to demonstrate effective immunotherapy against cancer through the systemic delivery of immune-stimulating chemotherapy combinations. A pH-responsive nanoplatform containing CaCO₃ was prepared by the double emulsion method, and mitoxantrone (MIT) and celastrol (CEL) were simultaneously encapsulated as immunogenic cell death (ICD) inducers. Due to the acid responsiveness of CaCO₃, the nanoparticles rapidly consume H⁺ to relieve the acidic tumor microenvironment and explosively release CEL and MIT, showing inherent immunomodulatory activity in collaborative tumor chemoimmunotherapy. MIT and CEL synergistically trigger stronger ICD by inducing tumor cells to release calreticulin (CRT), high mobility group box 1 protein (HMGB1). Following the intravenous administration of MCCaNPs, the local tumor microenvironment(TME) was reprogrammed in mice-bearing tumors. This reprogramming was characterized by a significant increase in the density of tumor-infiltrating cytotoxic T lymphocytes(CTLs), ultimately prolonging survival. Therefore, this research proposes a promising approach to trigger immunogenic cell death collaboratively, aiming to boost the tumor CTLs infiltration for anticancer immunotherapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124860"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500460","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}

{"title":"Multiple tail ionizable lipids improve in vivo mRNA delivery efficiency with biosafety","authors":"Chao Liu,&nbsp;Yuhao Jiang,&nbsp;Wenliang Xue,&nbsp;Jinyu Liu,&nbsp;Zihao Wang,&nbsp;Xinsong Li","doi":"10.1016/j.ijpharm.2024.124868","DOIUrl":"10.1016/j.ijpharm.2024.124868","url":null,"abstract":"<div><div>Ionizable lipid-based lipid nanoparticles (LNP) play a crucial role in the delivery of mRNA. The hydrophobic tail of ionizable lipid affects the formation of LNP and the release of mRNA. In this report, we focus on the effect of the number, chain length, and double bond number of the hydrophobic tail on the delivery efficiency. First, a series of ionizable lipids with two, three and four tails were synthesized and characterized featured with imidazole group as the head. The ionizable lipids derived LNP were prepared using a microfluidic co-mixing device, yielding particles primarily in the size range of 100 to 150 nm, with a polydispersity index (PDI) below 0.2. Screening identified ionizable lipids with four tails exhibiting superior delivery efficiency, of which U-15, U-17, U-18 and U-19 demonstrated the highest performance. Additionally, the U-19 significantly prolongs mRNA expression duration, and along with specific extrahepatic delivery effect compared to ALC-0315. Tissue slice tests on representatives (U-06: two tails, U-19: four tails, U-29: three tails) revealed no notable abnormalities. Analysis of immunogenicity, liver and kidney function tests indicated that all samples exhibited no evident immunogenicity or <em>in vivo</em> toxicity. Findings from tests on lysosome escape, cell transfection, and cytotoxicity revealed excellent <em>in vitro</em> delivery effectiveness. In summary, among the 35 imidazole-based ionizable lipids screened, optimal effects were exhibited by four tails, which providing a new strategy for the development of ionizable lipids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124868"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500465","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}

{"title":"Advances in conjugate drug delivery System: Opportunities and challenges","authors":"Yi-Shen Zhu ,&nbsp;Jiaqi Wu ,&nbsp;Feng Zhi","doi":"10.1016/j.ijpharm.2024.124867","DOIUrl":"10.1016/j.ijpharm.2024.124867","url":null,"abstract":"<div><div>Ideal drug delivery system is designed to accurately deliver the drug to its intended site. The development of conjugate drug delivery system introduces a novel pathway to precise drug delivery with advantages over traditional methods. The core of a conjugate drug delivery system comprises a molecule with two functional components, bounded by a linker structure. One component is responsible for delivering or stabilizing the conjugate, while the other is used to provide the therapeutic or diagnostic effects of the bioactivity. Conjugate drug delivery system improves patient health by maintaining the structural stability of drugs in molecular form, delivering therapeutics or diagnostic material to the target site, minimising off-target accumulation and promoting patient compliance. This system includes various types of drug conjugates that modulate drug pharmacokinetics, stability, absorption, and exposure in lesions and healthy tissues. In this review, we focus on the key characteristics and recent advances of various conjugate drug delivery systems and explore their mechanisms. We also point out the current challenges faced by conjugate drug delivery system and look forward to the future prospects.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124867"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500457","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}

{"title":"Nanostructured lipid carriers decorated with polyphosphate coated linear and loop cell-penetrating peptides","authors":"Ahmad Saleh ,&nbsp;Daniel Stengel ,&nbsp;Martyna Truszkowska ,&nbsp;Mariana Blanco Massani ,&nbsp;Gergely Kali ,&nbsp;Andreas Bernkop-Schnürch","doi":"10.1016/j.ijpharm.2024.124844","DOIUrl":"10.1016/j.ijpharm.2024.124844","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to evaluate the cellular uptake of nanostructured lipid carriers (NLCs) decorated with polyphosphate coated linear and loop cell-penetrating peptides (CPPs).</div></div><div><h3>Methods</h3><div>Linear-CPPs and loop-CPPs were synthesized via ring-opening polymerization and anchored on the surface NLCs, followed by coating with polyphosphate (PP). These nanocarriers (NCs) were characterized in terms of particle size, polydispersity index (PDI), and zeta potential. Cell viability and hemolysis, as well as enzyme-induced charge conversion via phosphate cleavage by free and membrane-bound intestinal alkaline phosphatase (IAP) were investigated. Cellular uptake studies by Caco-2 and HEK cells were quantitatively analyzed by flow cytometry and visualized by confocal microscopy.</div></div><div><h3>Results</h3><div>A shift in charge from positive to negative was obtained for both linear- and loop-CPPs-NLCs by coating with PP. PP-linear-CPPs-NLCs and PP-loop-CPPs-NLCs exhibited a particle size &lt; 270 nm and a PDI of approximately 0.3. They had a minor effect on cell viability and caused in a concentration of 0.1 % (m/v) around 10 % hemolysis within 24 h. IAP triggered the cleavage and release of monophosphate from the surface of NLCs causing charge conversion from –22.2 mV to + 5.3 mV (Δ27.5 mV) for PP-linear-CPPs-NLCs and from −19.2 mV to + 11.9 mV (Δ31.1 mV) for PP-loop-CPPs-NLCs. Inhibition of alkaline phosphatase activity on Caco-2 and HEK cells confirmed the involvement of this enzyme in charge conversion. PP-linear-CPPs-NLCs showed on Caco-2 cells a higher uptake than PP-loop-CPPs-NLCs, whereas on HEK cells uptake of both types of NLCs was on the same level. The results of cellular uptake were confirmed visually by confocal microscopy.</div></div><div><h3>Conclusion</h3><div>CPPs-NLCs coated with polyphosphate are a promising approach to overcome the polycationic dilemma and to enhance cellular uptake.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124844"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500466","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}

{"title":"Preparation, in vitro and in vivo assessment of novel carvacrol@pro-phytomicelles for the treatment of Salmonella enteritidis infection in mice","authors":"Zhengwei Cui ,&nbsp;Mengmeng Zhang ,&nbsp;Qingqian Meng ,&nbsp;Xianggen Wu ,&nbsp;Mengshuang Li","doi":"10.1016/j.ijpharm.2024.124861","DOIUrl":"10.1016/j.ijpharm.2024.124861","url":null,"abstract":"<div><div>In livestock and poultry farming, the use of antibiotics has been abused, which seriously endangers human health. Thus, antibiotic alternatives are urgently needed. The phytochemical carvacrol (CAR) has attracted attention as an antibiotic alternative due to its excellent antibacterial activity and anti-inflammatory activity. However, CAR has high volatility and low water solubility, which seriously affect its antibacterial activity. In this study, two plant-derived small-molecule phytochemicals—glycyrrhizin and rebaudioside A—were selected as nanocarriers for the preparation of a novel solid pro-phytomicelle formulation named as CAR@PP. Using a simple fabrication method, the encapsulation efficiency of CAR reached 98.74 ± 1.14 %. CAR@PP was found to rapidly dissolve in water, resulting in a transparent solution (named as CAR@M) and a 59-fold increase in solubility compared to CAR. CAR@M contained uniform nanoparticles with a particle size, polydispersity index, and zeta potential of 3.52 ± 0.93 nm, 0.17 ± 0.01, and −10.63 ± 0.45 mV, respectively. The in vitro antibacterial activity of CAR@M was evaluated, and the minimum inhibitory concentration for the tested strains was 125–250 μg/ml. The antibacterial mechanisms were found that CAR@M disrupted the bacterial wall and biomembranes and efficiently inhibited bacterial biofilm growth. To the in vivo activity evaluation, treatment with 50 mg/kg CAR@M could effectively improve bacterial liver abscesses, decrease the inflammatory cytokine levels in the liver and cecum, and reduce the bacterial load in the liver and feces in Salmonella enteritidis-infected mice. In conclusion, CAR@PP is a promising alternative to antibiotics in livestock and poultry farming warranting further research.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124861"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500467","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}

{"title":"Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch","authors":"Cong Li ,&nbsp;Donghui Hu ,&nbsp;Yafang Xu ,&nbsp;Heng Xu ,&nbsp;Liang Fang ,&nbsp;Guohua Wang ,&nbsp;Chao Liu","doi":"10.1016/j.ijpharm.2024.124862","DOIUrl":"10.1016/j.ijpharm.2024.124862","url":null,"abstract":"<div><div>This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, ¹³C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (<em>w/w</em>) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (<em>w/w</em>) as the matrix, and had a thickness of 90 μm. Compared with the oral group (<em>MRT</em>_0-t = 5.96 ± 0.97 h) and the control patch group (<em>MRT</em>_0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (<em>MRT</em>_0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124862"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500459","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}

{"title":"A microfluidic in vitro method predicting the fate of peptide drugs after subcutaneous administration","authors":"Marcus Wanselius ,&nbsp;Susanna Abrahmsén-Alami ,&nbsp;Belal I. Hanafy ,&nbsp;Mariarosa Mazza ,&nbsp;Per Hansson","doi":"10.1016/j.ijpharm.2024.124849","DOIUrl":"10.1016/j.ijpharm.2024.124849","url":null,"abstract":"<div><div>For many biopharmaceuticals, subcutaneous (sc) administration is the only viable route. However, there is no <em>in vitro</em> method available accurately predicting the absorption profiles of subcutaneously injected pharmaceuticals. In this work, we show that a recently developed microfluidics method for interaction studies (MIS) has the potential to be useful in this respect. The method utilises the responsiveness of polyelectrolyte microgel networks to oppositely charged molecules as a means to monitor the interaction between peptides and hyaluronic acid (HA), a major constituent of the subcutaneous extracellular matrix. We use the method to determine parameters describing the strength of interaction between peptide and HA as well as the peptide’s aggregation tendency and transport properties in HA networks. The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and <em>in vivo</em> absorption and bioavailability data from the literature. We show that both MIS and SCISSOR reveal differences in the peptides’ diffusivity and tendency to aggregate in the presence of HA. We show that MIS is particularly good at discriminating between peptides forming aggregates stabilised by non-electrostatic forces in the presence of HA, and peptides forming complexes stabilised by electrostatic interactions with HA. The method provides two parameters that can be used to quantify the peptides’ aggregation tendency, the one describing the peptide packing density in complexes with HA and the other the apparent diffusivity upon release in a medium of physiological ionic strength and pH. The order of the peptides when ranked by increasing binding strength at pH 7.4 determined with MIS is shown to be in agreement with the order when ranked by the apparent 1st order absorption rate constant (<em>k_a</em>) after sc administration in humans: lanreotide (Autogel) &lt; exenatide (IRF) &lt; AZD2820 &lt; pramlintide &lt; lanreotide (IRF) (IRF: Immediate release formulation). A correlation is found between the 1st order release rate constant determined with SCISSOR and <em>k_a</em> for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of <em>k_a</em> to the peptides’ charge is proposed.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124849"},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500447","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}