European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Study on the crystallinity of PEG on the crystalline size of flavonoids in a crystalline dispersion system","authors":"Hua Huang,&nbsp;Yong Zhang,&nbsp;Chunhui Hu","doi":"10.1016/j.ejpb.2024.114536","DOIUrl":"10.1016/j.ejpb.2024.114536","url":null,"abstract":"<div><div>Poor water solubility and low bioavailability of flavonoids present significant barriers to their development and application. To address these challenges, this study explores the use of crystalline solid dispersions (CSDs) to reduce drug crystalline size and enhance <em>in vivo</em> bioavailability. The CSDs were prepared using a spray-drying technique with chrysin (CHY) and quercetin (QUR) as model drugs and various molecular weights of polyethylene glycol (PEG) as carriers. The authors systematically investigated the factors influencing the interaction between flavonoids and PEG in CSDs. These factors included the relationships between intermolecular interactions and PEG molecular weight, crystallinity, microstructures such as crystalline domain size and crystal morphology of the flavonoids and PEG in CSDs, crystalline size of the drug in CSDs, and <em>in vitro</em> dissolution rate and <em>in vivo</em> pharmacokinetics. Our results indicated that the interaction between flavonoids and PEG in CSDs was influenced more by PEG crystallinity than by its molecular weight. Lower crystallinity of PEG, achieved through recrystallization, led to stronger intermolecular interactions with the drugs. Specifically, PEG8000 exhibited the lowest crystallinity, indicating a higher content of PEG in the amorphous state, which interacted more effectively with the amorphous drug in CSDs. This interaction significantly inhibited drug crystallization growth, resulting in a marked decrease in drug crystalline domain size and crystalline size. Consequently, PEG8000 was identified as the optimal carrier for preparing CSDs, achieving the best cumulative dissolution percentage. The QUR/PEG8000-CSD formulation increased the cumulative dissolution percentage and oral bioavailability of QUR by 18.76 and 20.66 times, respectively, compared to QUR alone. This study demonstrates that PEG crystallinity, following recrystallization, directly affects its intermolecular interactions with the drug, thereby impacting drug crystalline size and dissolution rate.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114536"},"PeriodicalIF":4.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497550","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":"Homogeneity and mechanical properties of orodispersible films loaded with pellets","authors":"Katarzyna Centkowska ,&nbsp;Martyna Szadkowska ,&nbsp;Marta Basztura ,&nbsp;Małgorzata Sznitowska","doi":"10.1016/j.ejpb.2024.114537","DOIUrl":"10.1016/j.ejpb.2024.114537","url":null,"abstract":"<div><div>Orodispersible<!--> <!-->films<!--> <!-->(ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. The production of ODFs with incorporated pellets may still be a challenging process due to problems to obtain proper homogeneity and deteriorating mechanical properties of the films with incorporated relatively big particles in high concentration. The goal of this work was to evaluate the possibility to achieve fast disintegrating ODFs with homogenously incorporated spherical granules without loss of required mechanical properties. Hypromellose films with incorporated placebo pellets (size 200 µm or 100 µm) in a content range of 20–45 % w/w were prepared by a solvent casting method. Planetary mixer (Thinky) was successfully applied for preparation of a homogeneous mass for casting. The suspended spherical solid particles caused dose and size dependent changes in the mechanical properties and disintegration behaviour of ODFs films, but only 100 µm pellets in concentration higher than 40 % reduced significantly the tear resistance. The films with the pellets disintegrated faster and the larger particles reduced the disintegration time by 60 %. Good homogeneity of pellets distribution, expressed as a number of the particles per unit area, was confirmed for films obtained with a gap height 500 or 800 µm.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114537"},"PeriodicalIF":4.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497549","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":"Evaluating surfactant effectiveness in preventing antibody adsorption directly on medical surfaces using a novel device","authors":"Rosa Álvarez-Palencia Jiménez ,&nbsp;Antoine Maze ,&nbsp;Franz Bruckert ,&nbsp;Fethi Bensaid ,&nbsp;Naila El-Kechai ,&nbsp;Marianne Weidenhaupt","doi":"10.1016/j.ejpb.2024.114539","DOIUrl":"10.1016/j.ejpb.2024.114539","url":null,"abstract":"<div><div>Biopharmaceuticals, specifically antibody-based therapeutics, have revolutionized disease treatment. Throughout their lifecycle, these therapeutic proteins are exposed to several stress conditions, for example at interfaces, posing a risk to the drug product stability, safety and quality. Therapeutic protein adsorption at interfaces may lead to loss of active product and protein aggregation, with potential immunogenicity risks. Non-ionic surfactants are commonly added in formulations to mitigate protein-surface interactions. However, their effectiveness varies with the monoclonal antibody (mAb), and model surface material. Extrapolating findings from model surfaces to real medical surfaces is challenging due to diverse properties.</div><div>This study pioneers the evaluation of surfactant effectiveness in preventing mAb adsorption directly on medical surfaces at the medical bag/formulation interface, utilizing the ELIBAG device. The adsorption of different protein modalities, mAbs and antibody-drug conjugate (ADC), using three surfactants (PS80, PS20, and P188), was examined across various medical surfaces, IV bags and manufacturing bags, and model surfaces. Our findings reveal that surfactants prevent mAb adsorption depending on the mAb modality, surfactant type and concentration, and surface material. This research underscores the importance of considering real medical surfaces in direct contact with formulations, offering insights for enhancing drug product development and ensuring material-protein compatibility in real world use.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114539"},"PeriodicalIF":4.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497546","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":"Development of transferosomes for topical ocular drug delivery of curcumin","authors":"Geisa Nascimento Barbalho ,&nbsp;Stefan Brugger ,&nbsp;Christian Raab ,&nbsp;Jara-Sophie Lechner ,&nbsp;Taís Gratieri ,&nbsp;Cornelia M. Keck ,&nbsp;Ilva D. Rupenthal ,&nbsp;Priyanka Agarwal","doi":"10.1016/j.ejpb.2024.114535","DOIUrl":"10.1016/j.ejpb.2024.114535","url":null,"abstract":"<div><h3>Background</h3><div>Transferosomes (TFS) are ultra-deformable elastic bilayer vesicles that have previously been used to enhance gradient driven penetration through the skin. This study aimed to evaluate the potential of TFS for topical ocular drug delivery and to compare their penetration enhancing properties in different ocular tissues.</div></div><div><h3>Methods</h3><div>Curcumin-loaded TFS were prepared using Tween 80 as the edge activator. Drug release and precorneal retention of the TFS were evaluated in vitro, while their ocular biocompatibility and bioavailability were evaluated ex vivo using a curcumin solution in medium chain triglycerides as the oily control.</div></div><div><h3>Results</h3><div>The TFS had a narrow size distribution with a particle size less than 150 nm and an entrapment efficiency greater than 99.96 %. Burst release from the TFS was minimal and the formulation showed good corneal biocompatibility. Moreover, enhanced corneal and conjunctival drug penetration with significantly greater and deeper drug delivery was observed with TFS.</div></div><div><h3>Conclusion</h3><div>TFS offer a promising platform for ocular delivery of hydrophobic drugs. This study, for the first time, elucidates the effect of tissue morphology and osmotic gradients on drug penetration in different ocular tissues.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114535"},"PeriodicalIF":4.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461138","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":"Freeze-drying-induced mutarotation of lactose detected by Raman spectroscopy","authors":"Julia Monola ,&nbsp;Elle Koivunotko ,&nbsp;Jacopo Zini ,&nbsp;Akseli Niemelä ,&nbsp;Artturi Koivuniemi ,&nbsp;Aleksi Kröger ,&nbsp;Ossi Korhonen ,&nbsp;Sami Valkonen ,&nbsp;Arto Merivaara ,&nbsp;Riina Harjumäki ,&nbsp;Marjo Yliperttula ,&nbsp;Jere Kekkonen","doi":"10.1016/j.ejpb.2024.114534","DOIUrl":"10.1016/j.ejpb.2024.114534","url":null,"abstract":"<div><div>Freeze-drying enables delicate, heat-sensitive biomaterials to be stored in a dry form even at room temperature. However, exposure to physicochemical stress induced by freeze-drying presents challenges for maintaining material characteristics and functionality upon reconstitution, for which reason excipients are required. Although wide variety of different excipients are available for pharmaceutical applications, their protective role in the freeze-drying is not yet fully understood. In this study, our aim was to use molecular dynamics simulations to screen the properties of different sugars and amino acids, which could be combined with plant-based nanofibrillated cellulose (NFC) hydrogel to provide protective matrix system for future freeze-drying for pharmaceuticals and biologics. The changes in the NFC-based formulations before and after freeze-drying and reconstitution were evaluated using non-invasive Timegate PicoRaman spectroscopy and traditional characterization methods. We continued to the freeze-drying with the NFC hydrogel formulations including lactose with and without glycine, which showed the highest attraction preferences on NFC surface <em>in silico.</em> This formulation enabled successful freeze-drying and subsequent reconstitution with preserved physicochemical and rheological properties. Raman spectroscopy gave us insights of the molecular-level changes during freeze-drying, especially the mutarotation of lactose. This research showed the potential of integrating <em>in silico</em> screening and non-invasive spectroscopical method to design novel biomaterial-based formulations for freeze-drying. The research provided insights of the molecular-level interactions and orientational changes of the excipients, which might be crucial in future freeze-drying applications of pharmaceuticals and biologics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114534"},"PeriodicalIF":4.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461139","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":"Simvastatin and adenosine-co-loaded nanostructured lipid carriers for wound healing: Development, characterization and cell-based investigation","authors":"Regina Gomes Daré ,&nbsp;Ana Beatriz Chieco Costa ,&nbsp;Tereza Silva Martins ,&nbsp;Luciana B. Lopes","doi":"10.1016/j.ejpb.2024.114533","DOIUrl":"10.1016/j.ejpb.2024.114533","url":null,"abstract":"<div><div>Chronic wounds represent a significant global health burden, characterized by delayed skin healing and associated comorbidities. The present study aimed to develop nanostructured lipid carriers (NLCs) as a topical delivery system for the co-administration of simvastatin and adenosine to address chronic wound management. The rationale behind the co-delivery approach was to mitigate the cytotoxicity associated with high-dose simvastatin, while preserving its therapeutic benefits through a potential synergistic or additive effect. A significant challenge in the development of these NLCs was the encapsulation of the highly hydrophilic adenosine within the hydrophobic lipid matrix. The NLCs were prepared using a hot homogenization-sonication method with a double emulsion technique and optimized through a series of formulation trials, employing various surfactants, solid and liquid lipids, to achieve efficient drug encapsulation, particularly for the hydrophilic adenosine. Optimized formulations F5- and F10-S/A 0.6 %/2 % (containing 0.6 % simvastatin and 2 % adenosine), exhibited promising physicochemical properties. The main difference was the liquid lipid used: F5 contained Miglyol 810 N, while F10 contained Capmul MCM C-8. Both formulations displayed a mean particle size below 230 nm, a polydispersity index (PDI) of approximately 0.2, and a zeta potential around –22 mV. While simvastatin association efficiency (AE) was nearly 100 %, adenosine AE was higher for F10 (24 %), compared to F5 (13.5 %). F5 demonstrated superior stability compared to F10, maintaining consistent particle size and PDI over a 60-day period. Formulation F5 also demonstrated superior cell-based <em>in vitro</em> performance compared to F10, with higher cell viability (MTT assay), greater cell proliferation induction (SRB assay), and enhanced cell proliferation and migration in the wound-scratch assay. While F10 displayed higher adenosine AE, F5 excelled in terms of stability and biological activity. The slight increase in intracellular reactive oxygen species levels observed with F5 may contribute to its enhanced proliferative effects. In-depth characterization revealed that F5 comprised spherical nanoparticles, and thermal analysis indicated no significant changes in the nanocarrier structure upon drug encapsulation. Additionally<em>, ex vivo</em> permeability study demonstrated superior skin retention of both simvastatin and adenosine for F5 compared to an emulsion control. Overall, the F5 nanocarrier demonstrated suitable physicochemical properties, cellular biocompatibility, induction of cell proliferation and migration events, and drug retention capacity in the skin layers, indicating its potential as a promising topical treatment for difficult-to-heal wounds.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114533"},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461140","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":"Unleashing the antitumor power of cyclophosphamide by arabinogalactan and aptamer conjugation","authors":"Tatiana N. Zamay ,&nbsp;Olga S. Kolovskaya ,&nbsp;Galina S. Zamay ,&nbsp;Andrey K. Kirichenko ,&nbsp;Natalia A. Luzan ,&nbsp;Sergey S. Zamay ,&nbsp;Nadezhda A. Neverova ,&nbsp;Elena N. Medvedeva ,&nbsp;Vasilii A. Babkin ,&nbsp;Dmitry V. Veprintsev ,&nbsp;Irina A. Shchugoreva ,&nbsp;Anna S. Kichkailo","doi":"10.1016/j.ejpb.2024.114531","DOIUrl":"10.1016/j.ejpb.2024.114531","url":null,"abstract":"<div><div>Cyclophosphamide (CPA) (2-oxo-2-di(β-chloroethyl)amino tetrahydro-2,1,3-phosphoxazine) is an alkylating cytostatic compound with a broad spectrum of antitumor activity. Despite its efficacy, the clinical application of CPA is hindered by the significant occurrence of adverse side effects. To address these limitations, a promising approach involves the mechanochemical treatment of CPA with arabinogalactan (AG) to facilitate the dispersion of the drug within the AG matrix. AG stands out from other polymers due to its uniformity, low molecular weight, water solubility, and ability to form drug conjugates, thereby enhancing their therapeutic potency. Moreover, AG possesses immune-modulating properties that have the potential to counteract the immunosuppressive effects induced by CPA. By means of mechanical treatment, we successfully obtained CPA-AG complexes with a CPA:AG ratio of 1:10. These complexes were further modified with As42 aptamers that specifically target Erlich ascites cells. Aptamers, a novel class of oligonucleotide ligands obtained through SELEX technology, possess high affinity and specificity for binding to various receptors. An ascitic form of Ehrlich carcinoma was chosen as an in vitro and <em>in vivo</em> tumor model due to its notable drug resistance. In vitro and <em>in vivo</em> evaluations were conducted to compare the antitumor activity of both the CPA-AG and CPA-AG-As42 complexes with pure CPA. In vitro experiments revealed that the CPA-AG complex displayed superior antitumor activity compared to pure CPA, leading to complete tumor cell death primarily through necrosis. Notably, no toxic effects were observed with the CPA-AG and CPA-AG-As42 complexes, and they significantly prolonged the lifespan of tumor-bearing mice by more than 3.5 times. Histological studies further supported the antitumor efficacy of these complexes. These results underscore the potential of utilizing CPA-AG mechanocomposites, functionalized with aptamers, for the targeted delivery of CPA to tumors.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114531"},"PeriodicalIF":4.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445257","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":"Development and characterization of novel fast-dissolving pentobarbital suppositories for pediatric procedural sedation and comparison with lipophilic formulations","authors":"Aurelien Freisz ,&nbsp;Imen Dhifallah ,&nbsp;Yoann Le Basle ,&nbsp;Mireille Jouannet ,&nbsp;Philip Chennell ,&nbsp;Ghislain Garrait ,&nbsp;Eric Beyssac ,&nbsp;Yassine Bouattour ,&nbsp;Valérie Sautou","doi":"10.1016/j.ejpb.2024.114532","DOIUrl":"10.1016/j.ejpb.2024.114532","url":null,"abstract":"<div><div>For pediatric radiological procedures (RP), pentobarbital sodium (PNa) can be used orally or rectally to replace intravenous anesthesia. Since no commercial PNa suppositories exist, they must be prepared by compounding pharmacies. This study aims to develop fast-dissolving PNa suppositories for fast pharmacological activity during RP. We prepared gelatin (G), gelatin/polyethylene glycol 4000 (GP), and polyethylene glycol 4000 (P) suppositories, with and without pH adjustment, and assessed their dosage uniformity (DU), softening time, rupture resistance, and <em>in-vitro</em> dissolution. An optimal formulation was selected, and PNa release was compared to that of fat-based suppositories using dissolution tests. Additionally, the quality control process (analytical performance, safety/eco-friendliness and productivity/practical effectiveness) of these formulas were compared using a RGB method. All hydrophilic formulas (HF) met the DU requirement (AV &lt; 8 %) except for P (AV 15.62 ± 4 %). pH adjustment enhanced G and GP suppositories resistance to 2.2 ± 0.2 kg and 2.0 ± 0.3 kg, respectively, and allowed <strong>100 % release</strong> of PNa in under 10 min. In contrast, lipophilic formulas released less than 80 % of PNa at best after 120 min. These results show the biopharmaceutical suitability of HF for RP compared to lipophilic ones, but a pharmacokinetic study is needed to confirm data.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114532"},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433122","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":"Authors’ reply to comments on “Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt”","authors":"Lixin Liu,&nbsp;Yuning Wang,&nbsp;Jiuyi Sun,&nbsp;Yunan Zhang,&nbsp;Xiangyu Zhang,&nbsp;Lili Wu,&nbsp;Yingli Liu,&nbsp;Xuan Zhang,&nbsp;Yidi Xia,&nbsp;Qiumei Zhang,&nbsp;Ning Gao","doi":"10.1016/j.ejpb.2024.114519","DOIUrl":"10.1016/j.ejpb.2024.114519","url":null,"abstract":"<div><div>This article responds to Dr. Shayanfar’s comment “Improvement of photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesizing fleroxacin-D-tartaric acid pharmaceutical salt”. We rationalized and explained the solubility study portion of the published novel pharmaceutical salt (fleroxacin-D-tartaric acid, FL-D-TT). This confirms that the results of the solubility studies of fleroxacin (FL) and its pharmaceutical salt (FL-D-TT) in our published articles are true and accurate and consistent with the theoretical analysis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114519"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406267","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":"Formulation strategies, preparation methods, and devices for pulmonary delivery of biologics","authors":"Kai Berkenfeld ,&nbsp;Simone Carneiro ,&nbsp;Carolina Corzo ,&nbsp;Flavia Laffleur ,&nbsp;Sharareh Salar-Behzadi ,&nbsp;Benjamin Winkeljann ,&nbsp;Golbarg Esfahani","doi":"10.1016/j.ejpb.2024.114530","DOIUrl":"10.1016/j.ejpb.2024.114530","url":null,"abstract":"<div><div>Biological products, including vaccines, blood components, and recombinant therapeutic proteins, are derived from natural sources such as humans, animals, or microorganisms and are typically produced using advanced biotechnological methods. The success of biologics, particularly monoclonal antibodies, can be attributed to their favorable safety profiles and target specificity. However, their large molecular size presents significant challenges in drug delivery, particularly in overcoming biological barriers. Pulmonary delivery has emerged as a promising route for administering biologics, offering non-invasive delivery with rapid absorption, high systemic bioavailability, and avoidance of first-pass metabolism. This review first details the anatomy and physiological barriers of the respiratory tract and the associated challenges of pulmonary drug delivery (PDD). It further discusses innovations in PDD, the impact of particle size on drug deposition, and the use of secondary particles, such as nanoparticles, to enhance bioavailability and targeting. The review also explains various devices used for PDD, including dry powder inhalers (DPIs) and nebulizers, highlighting their advantages and limitations in delivering biologics. The role of excipients in improving the stability and performance of inhalation products is also addressed. Since dry powders are considered the suitable format for delivering biomolecules, particular emphasis is placed on the excipients used in DPI development. The final section of the article reviews and compares various dry powder manufacturing methods, clarifying their clinical relevance and potential for future applications in the field of inhalable drug formulation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114530"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406269","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}