RSC Pharmaceutics最新文献

{"title":"Structure–activity relationships of DNA nanocarriers based on the amphipathic cell penetrating peptide transportan 10†","authors":"Lucas Rodrigues de Mello, Tâmisa Seeko Bandeira Honda, Sang Won Han, Valeria Castelletto, Ian William Hamley, Ly Porosk, Ülo Langel and Emerson Rodrigo da Silva","doi":"10.1039/D4PM00065J","DOIUrl":"https://doi.org/10.1039/D4PM00065J","url":null,"abstract":"<p >Cell penetrating peptides (CPPs) have emerged as promising materials for the fabrication of synthetic nanovectors endowed with potential for improving the future landscape of gene therapy. A group of well-studied CPPs includes the transportan family, comprised of chimeric molecules combining segments derived from the antimicrobial wasp-venom mastoporan and the neuropeptide galanin. The success of these CPPs is supported by their effective use as the base for commercial peptide-based transfection reagents. Herein, we present a comprehensive study of the structure of peptiplexes formed between DNA fragments and transportan 10, a prototype example of amphipathic CPP. We conducted a thorough analysis of the self-aggregation of TP10, its secondary structure, and revealed details of its interaction with DNA. We employed atomic force microscopy-based nanospectroscopy to obtain single-particle data that revealed details of the conformations assumed by the peptide and DNA in the inner structure of nanoassemblies with different morphologies. Our structural results showed that TP10 exhibits self-aggregation capabilities and a strong propensity to assume α-helical conformations upon association with DNA strands. This behavior contrasts with that of prototype CPPs such as TAT-HIV and penetratin, potentially explaining why peptiplexes based on transportans demonstrate increased uptake compared to their cationic counterparts. Also, single-particle spectroscopy indicated that the secondary structure in peptiplexes is strongly dependent on the size and shape, reinforcing that controlled self-assembly is crucial for optimizing CPP-based nanotherapeutics. The peptiplexes were also evaluated for cell uptake efficiency and kinetics, revealing a logistic time–response increase in permeability, suggestive of cooperativeness. We anticipate that the findings presented here might contribute to refining structure–activity relationships of peptiplexes based on amphipathic CPPs, assisting the optimization of products based on this relevant class of CPPs with potential applications in therapeutic delivery systems.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 976-993"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00065j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target-selective cytosolic delivery of cargo proteins using the VHH-presented OLE-ZIP capsules†","authors":"Kousuke Takahashi, Yasumichi Inoue, Shigeaki Hida, Ryuki Hosoda, Naoki Umezawa, Isamu Akiba, Mitsuo Umetsu and Toshihisa Mizuno","doi":"10.1039/D4PM00069B","DOIUrl":"https://doi.org/10.1039/D4PM00069B","url":null,"abstract":"<p >In the pursuit of a new generation of protein pharmaceuticals, the efficient delivery of these therapeutics into cells stands out as a crucial challenge. In this study, we have developed a novel approach utilizing protein capsules modified with VHH antibodies as cytosolic carriers for protein pharmaceuticals. For the protein capsule component, we opted for the OLE-ZIP protein capsules, which can be prepared from the amphiphilic two-helix bundled protein OLE-ZIP using the water-in-oil (w/o) emulsion method. The spacious interior of the OLE-ZIP capsules allows for the stable encapsulation of over 200 molecules of protein pharmaceuticals, such as RNase A and Cre recombinase, in one capsule. By presenting the VHH antibody with an affinity for cell-type-specific receptors such as the epidermal growth factor receptor (EGFR) on the capsule surface, we achieved cell-type selective endocytic uptake in A431 cell lines (high expression level of EGFR) over NHDF and MCF-7 cells (normal expression level of EGFR). This selective uptake was followed by the subsequent release of the encapsulated protein pharmaceuticals into the cytosol of the target cells. Unlike our previous version of the OLE-ZIP protein capsules modified with IgG antibodies, cytosolic delivery of pharmaceutical proteins was little impacted by the presence of other IgGs, which are abundant in the bloodstream. This improved characteristic suggests potential advantages for practical applications, including intravenous administration.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 786-796"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00069b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionalized SBA-15: engineering, detailed study on release and kinetics of alendronate as well as its anti-tumour properties towards osteosarcoma","authors":"Anjali Patel and Shivangi Mehta","doi":"10.1039/D4PM00078A","DOIUrl":"https://doi.org/10.1039/D4PM00078A","url":null,"abstract":"<p >The present work deals with designing a biocompatible controlled drug delivery system (DDS) based on 12-tungstophosphoric acid (TPA)-functionalized SBA-15 for anti-osteoporotic drug alendronate sodium (ALD) and its characterization using different physicochemical techniques such as TGA, FT-IR spectroscopy, XRD, N<small>₂</small> adsorption measurements, HRTEM, and SEM. The designed DDS, ALD/TPA/SBA-15, was assessed for its drug delivery potential by carrying out <em>in vitro</em> drug release in simulated body fluid (pH 7.4, 37 °C) under stirring conditions as well as for the dissolution study. Release kinetics and mechanisms using zero order, first order, and Higuchi model were also carried out. Further, the release profile of the designed DDS was compared with the available marketed formulation (Osteofos), and ALD/TPA/SBA-15 shows a more controlled release. To explore the direct anti-tumour potency of ALD on osteosarcoma cells, an MTT assay was carried out at different concentrations, and the results show concentration-dependent inhibition of osteosarcoma cell proliferation.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 797-805"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00078a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids†","authors":"Robert J. Cavanagh, Saif Baquain, Cameron Alexander, Oren A. Scherman and Ruman Rahman","doi":"10.1039/D4PM00177J","DOIUrl":"https://doi.org/10.1039/D4PM00177J","url":null,"abstract":"<p >Drug combinations have been shown to be highly effective in many cancer therapies but the ratios of the individual drugs must be adjusted carefully and formulated appropriately to ensure synergistic action. Here we assessed combinations of doxorubicin and gemcitabine for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). 2D and 3D spheroid <em>in vitro</em> models of GBM were generated from patient-derived glioblastoma cells resected from brain tumour cores and invasive margins. Drug combinations were screened for synergy using the Chou–Talalay method and mechanisms of action investigated using measures of caspase 3/7-mediated apoptosis and γH2AX-mediated DNA damage. Single drug and drug combinations were formulated in a supramolecular hydrogel based on a peptide-functionalised hyaluronic acid backbone dynamically linked by cucurbit[8]uril-mediated host–guest interactions as an implantable drug-delivery vehicle. Drug efficacy data from <em>in vitro</em> assays demonstrated synergistic activity with doxorubicin and gemcitabine combinations in a molar ratio-dependent manner. These compounds were included in the drug screen as exemplars of DNA intercalators and nucleoside analogue respectively. Consistent with this, enhanced apoptosis and DNA damage were also observed in a synergistic manner. Overall, these drug-loaded hydrogels demonstrated potency and maintenance of synergy with drug-combination hydrogels, in an easy-to-administer <em>in situ</em> gelling formulation suitable for post-resection delivery to prevent GBM recurrence.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 742-754"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00177j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrospun dressings with a dual release functionality of two anti-inflammatory active ingredients†","authors":"Anna-Lena Gürtler, Jonathan P. Sirois, Julia C. Lang, Keira Melican, Thomas Rades and Andrea Heinz","doi":"10.1039/D4PM00147H","DOIUrl":"https://doi.org/10.1039/D4PM00147H","url":null,"abstract":"<p >Inflammatory skin conditions are commonly treated using topical semi-solid formulations such as creams, ointments, or gels. However, the use of such formulations is often connected to poor patient adherence due to the greasiness of the formulations and the need to apply different products multiple times a day. To overcome this challenge, we aimed to develop an anti-inflammatory electrospun dressing containing two active ingredients with a reduced application frequency of once a day, enhancing the treatment comfort for the patients. Salicylic acid and hydrocortisone were combined in a polycaprolactone-based electrospun fiber dressing with a dual release functionality, featuring both a burst and sustained release of salicylic acid and hydrocortisone, respectively. While electrospun dressings have been extensively studied in terms of their material characteristics and drug release behavior, few studies have explored their release behavior in conjunction with their skin permeation performance. Our study bridges this gap by providing and comparing both drug release and skin permeation data. We found a rapid release of salicylic acid and a delayed release of hydrocortisone in our layer-by-layer system. Although significantly less hydrocortisone was released from the layer-by-layer system in the permeation studies compared to the release studies, hydrocortisone still permeated through different skin layers. Moreover, we verified the anti-inflammatory properties of the electrospun dressing in studies on human keratinocytes and human skin. Special emphasis was placed on comparing results with standard pharmaceutical formulations, namely a hydrocortisone cream and a salicylic acid ointment. Permeation studies showed higher hydrocortisone penetration into the skin from the layer-by-layer fiber dressing compared to standard formulations. Our findings highlight the feasibility of combining multiple drugs in a single electrospun fiber system, while achieving controlled release behavior through tuning the composition of the drug delivery system. Our study moreover confirms that conducting permeation experiments alongside release studies is crucial for correlating results and evaluating the effectiveness of a drug delivery system.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 570-580"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00147h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macauba oil carried by polymeric micelles reduces migration and proliferation of triple-negative breast cancer cells","authors":"Davi T. Aleixo, Ana C. M. Gualberto, Ana B. C. dos S. Valle, Luan C. da Silva, Kézia C. B. Ferreira, Ari S. de O. Lemos, Rodrigo L. Fabri, Guilherme D. Tavares, Maurílio de S. Cazarim, Jacy Gameiro and Frederico Pittella","doi":"10.1039/D4PM00158C","DOIUrl":"https://doi.org/10.1039/D4PM00158C","url":null,"abstract":"<p >Triple-negative breast cancer (TNBC) accounts for about 10–15% of all breast cancer cases, often affecting younger women and those with a BRCA1 mutation. It is more aggressive and has a higher recurrence risk within the first few years after diagnosis. Due to its aggressive nature, limited treatment options, and drug resistance, alternative strategies are urgently needed. In this context, Macauba (<em>Acrocomia aculeata</em>) is a South American palm with antioxidant-rich fruits containing fatty acids, carotenoids, and phenolic compounds, which can remove reactive oxygen species (ROS) and protect cells. Our study focused on creating Macauba pulp oil-loaded polymeric micelles (PM-MO) and assessing their impact on triple-negative breast cancer cells in terms of cytotoxicity, antiproliferation, and antimigration. Before formulating PM-MO, we conducted chemical characterization and testing of Macauba oil. Further, PM-MO presented hydrodynamic diameters of 105 nm, polydispersity index (PdI) of 0.12 and Zeta potential of −17.5 mV. PM-MO showed enhanced cytotoxicity against triple negative breast cancer cells after 48h and 72h, while no toxicity was observed on non-tumor cells. The clonogenicity assay showed a reduction in the formation of cell colonies ranging from 97% to 81.9% at the highest concentration of PM-MO. Treatment with PM-MO reduced breast cancer cell migration <em>in vitro</em>, indicating potential as an anti-metastatic agent. We conclude that the method used to produce PM-MO yielded well-sized nanoparticles with uniform distribution. Results from cell viability, proliferation, and migration tests highlight its potential for future <em>in vivo</em> trials against triple-negative breast cancer.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 524-535"},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00158c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The etiology, pathogenesis, treatment, and development of transdermal drug delivery systems for rheumatoid arthritis","authors":"Mirza Muhammad Faran Ashraf Baig, Chi Hin Kwan, Hongkai Wu and Sek Ying Chair","doi":"10.1039/D4PM00085D","DOIUrl":"https://doi.org/10.1039/D4PM00085D","url":null,"abstract":"<p >Rheumatoid arthritis (RA) is a long-term autoimmune disease that causes irreversible deformity of joints and disability of body parts. The symptoms include synovial tissue inflammation and cartilage and bone damage. To reduce the inflammation, therapeutic drugs are often used to target and limit the inflammation factor. Nonetheless, there are significant problems with the treatment such as a first-pass effect, gastrointestinal side effects, skin stratum corneum barrier, <em>etc</em>. Hence, a transdermal delivery system (TDDS) is applied for the treatment of rheumatoid arthritis as it increases the effectiveness of the drugs by overcoming the difficulties mentioned above. This paper reviews the research progress of transdermal drug delivery for the treatment of rheumatoid arthritis and explores the details of dosage forms such as gel, patch, drug microneedles, nanostructured lipid carriers and drug-loaded electrospun nanofibers, which provide numerous ideas for these dosage forms in RA treatment when using transdermal drug delivery methods.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 592-607"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00085d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of emulsion and spray methods for fabrication of rapamycin-loaded acetalated dextran microparticles†","authors":"Stephen A. Ehrenzeller, Nicole Rose Lukesh, Rebeca T. Stiepel, Denzel D. Middleton, Steven M. Nuzzolo, Aliyah J. Tate, Cole J. Batty, Eric M. Bachelder and Kristy M. Ainslie","doi":"10.1039/D4PM00054D","DOIUrl":"https://doi.org/10.1039/D4PM00054D","url":null,"abstract":"<p >Rapamycin (rapa), an immunosuppressive medication, has demonstrated considerable effectiveness in reducing organ transplant rejection and treating select autoimmune diseases. However, the standard oral administration of rapa results in poor bioavailability, broad biodistribution, and harmful off-target effects, necessitating improved drug delivery formulations. Polymeric microparticles (MPs) are one such solution and have demonstrated promise in pre-clinical studies to improve the therapeutic efficacy of rapa. Nevertheless, MP formulations are highly diverse, and fabrication method selection is a critical consideration in formulation design. Herein, we compared common fabrication processes for the development of rapa-loaded MPs. Using the biopolymer acetalated dextran (Ace-DEX), rapa-loaded MPs were fabricated by both emulsion (homogenization and sonication) and spray (electrospray and spray drying) methods, and resultant MPs were characterized for size, morphology, surface charge, and drug release kinetics. MPs were then screened in LPS-stimulated macrophages to gauge immunosuppressive efficacy relative to soluble drug. We determined that homogenized MPs possessed the most optimal combination of sizing, tunable drug release kinetics, and immunosuppressive efficacy, and we subsequently demonstrated that these characteristics were maintained across a range of potential rapa loadings. Further, we performed <em>in vivo</em> trafficking studies to evaluate depot kinetics and cellular uptake at the injection site after subcutaneous injection of homogenized MPs. We observed preferential MP uptake by dendritic cells at the depot, highlighting the potential for MPs to direct more targeted drug delivery. Our results emphasize the significance of fabrication method in modulating the efficacy of MP systems and inform improved formulation design for the delivery of rapa.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 727-741"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00054d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical salts of azole anti-fungal drugs: physicochemical behaviour and activity studies†","authors":"Hafsa Qadri, Asif A. Malik, Aadil A. Ahangar, Manzoor Ahmad Mir, Ajiaz A. Dar and Abdul Haseeb Shah","doi":"10.1039/D4PM00003J","DOIUrl":"https://doi.org/10.1039/D4PM00003J","url":null,"abstract":"<p >Pharmaceutical cocrystal engineering is a potential and growing strategy for modulating the physicochemical and pharmacokinetic properties of drug molecules. This study aims to study the new solid forms of miconazole (MIC) and ketoconazole (KTC) prepared through the crystal engineering method of crystallization. Utilizing the understanding of the sulfonate-pyridinium synthon, molecular salts of MIC and KTC with naphthalene disulfonic acid (NDSA-2H) have been prepared and characterized through thermal, spectroscopic, microscopic, and diffraction methods. Both molecular salts, <em>i.e.</em>, MIC-C and KTC-C, have been obtained as crystalline solids and their phase purity and formation have been established through diffraction studies. The new drug forms exhibit augmented thermal stability and aqueous solubility. Powder dissolution studies in an aqueous medium at pH 2 and pH 7 indicate a significant increase in thermal stability and aqueous solubility of the new drug forms compared to their drug precursors. Structural investigation of MIC-C validates the formation of the ionic sulfonate-pyridinium synthon involving proton transfer resulting in charge development, leading to enhancement in the physicochemical properties. <em>In vitro</em> studies show that KTC-C in addition to retaining most of the biological activities possesses antifungal potential comparable to that of the standard drug since it inhibited the growth of tested <em>Candida</em> strains without showing enhancement in host toxicity. Both the designed salts exhibit fluorescence properties inside <em>Candida</em> cells (in contrast to the standard drugs).</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 705-715"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00003j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of leucine as an aerosolization enhancer on the bioactivity of spray dried viral-vectored vaccines for inhalation","authors":"Varsha Singh, Myrna Dolovich, Zhou Xing, Emily D. Cranston and Michael R. Thompson","doi":"10.1039/D4PM00079J","DOIUrl":"https://doi.org/10.1039/D4PM00079J","url":null,"abstract":"<p >Aerosolization enhancers, like <small>L</small>-leucine, can improve deep-lung deposition of inhalable dry powders although the implications of their use have not yet been evaluated for sensitive biologics like viral vectored vaccines. This study investigates the effect of <small>L</small>-leucine concentrations (0–50 wt%) as an added component to the viral-encapsulating matrix comprised of mannitol and dextran, on aerosolization relative to bioactivity of spray dried human serotype 5 adenovirus. Modelling the intended purpose of inhalation, the aerodynamic properties (fine particle fraction and mass median aerodynamic diameter) of the powders were analyzed using a Next Generation Impactor. Overall, increasing the <small>L</small>-leucine concentration in the spray dried formulations improved the fine particle fraction (&gt;40%) and reduced the aerodynamic diameter (&lt;5 μm). However, bioactivity was negatively affected by the presence of <small>L</small>-leucine in the formulation and that demanded deeper investigation. The root cause for the declining bioactivity was finally attributed to aggregation of the adenovirus induced by <small>L</small>-leucine in the feed solution prior to spray drying, which was determined using a qViro-X particle counter. The intent of this study was to emphasize that advantages and disadvantages will exist with additives like an aerosolization enhancer, for this relatively new class of vaccines.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 775-785"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00079j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}