Drug Delivery最新文献

{"title":"Quantitative analysis of therapeutic proteins in biological fluids: recent advancement in analytical techniques.","authors":"Jae Geun Song, Kshitis Chandra Baral, Gyu-Lin Kim, Ji-Won Park, Soo-Hwa Seo, Da-Hyun Kim, Dong Hoon Jung, Nonye Linda Ifekpolugo, Hyo-Kyung Han","doi":"10.1080/10717544.2023.2183816","DOIUrl":"10.1080/10717544.2023.2183816","url":null,"abstract":"<p><p>Pharmaceutical application of therapeutic proteins has been continuously expanded for the treatment of various diseases. Efficient and reliable bioanalytical methods are essential to expedite the identification and successful clinical development of therapeutic proteins. In particular, selective quantitative assays in a high-throughput format are critical for the pharmacokinetic and pharmacodynamic evaluation of protein drugs and to meet the regulatory requirements for new drug approval. However, the inherent complexity of proteins and many interfering substances presented in biological matrices have a great impact on the specificity, sensitivity, accuracy, and robustness of analytical assays, thereby hindering the quantification of proteins. To overcome these issues, various protein assays and sample preparation methods are currently available in a medium- or high-throughput format. While there is no standard or universal approach suitable for all circumstances, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay often becomes a method of choice for the identification and quantitative analysis of therapeutic proteins in complex biological samples, owing to its high sensitivity, specificity, and throughput. Accordingly, its application as an essential analytical tool is continuously expanded in pharmaceutical R&D processes. Proper sample preparation is also important since clean samples can minimize the interference from co-existing substances and improve the specificity and sensitivity of LC-MS/MS assays. A combination of different methods can be utilized to improve bioanalytical performance and ensure more accurate quantification. This review provides an overview of various protein assays and sample preparation methods, with particular emphasis on quantitative protein analysis by LC-MS/MS.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2183816"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442237","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":"Andrographolide nanophytosomes exhibit enhanced cellular delivery and pro-apoptotic activities in HepG2 liver cancer cells.","authors":"Thikryat Neamatallah, Azizah M Malebari, Abdulmohsin J Alamoudi, Syed Nazreen, Mohammad Mahboob Alam, Hawazen H Bin-Melaih, Osama A Abuzinadah, Shaimaa M Badr-Eldin, Gharam Alhassani, Lamar Makki, Mohammed Z Nasrullah","doi":"10.1080/10717544.2023.2174209","DOIUrl":"10.1080/10717544.2023.2174209","url":null,"abstract":"<p><p>Andrographolide (AG), a major active constituent of <i>Andrographis paniculata,</i> is known to hinder proliferation of several types of cancer cells. However, its poor solubility and cellular permeability restrict its use in clinical applications. In this study, AG-loaded phytosomes (AG-PTMs) were formulated and optimized with respect to particle size using l-α-phosphatidylcholine (PC):AG ratio and sonication time (ST) as independent variables. The optimized formula was prepared at 1:2.7 for AG:PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm, polydispersity index (PDI) of 0.310 and entrapment efficiency of 72.20 ± 4.53. Also, the prepared formula showed a slow release of AG over 24-h period. The antiproliferative activity of AG-PTMs was investigated against the liver cancer cell line HepG2. AG-PTMs significantly repressed the growth of HepG2 cells with an IC₅₀ value of 4.02 ± 0.14 µM. AG uptake by HepG2 cells was significantly enhanced in incubations containing the optimized formula. AG-PTMs also caused G2-M cell cycle phase arrest and increased the fraction of apoptotic cells in pre-G1 phase. These effects were associated with induction of oxidative stress and mitochondrial dysfunction. In addition, AG-PTMs significantly upregulated mRNA expression of <i>BAX</i> and downregulated that of <i>BCL2.</i> Furthermore, AG-PTMs significantly enhanced the concentration of caspase-3 in comparison to raw AG. These data indicate that the phytosomal delivery of AG significantly inhibited HepG2 cell proliferation through enhanced cellular uptake, arresting cell cycle at the G2-M phase and inducing mitochondrial-dependent apoptosis.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2174209"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10733957","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":"Novel nano-carriers with N-formylmethionyl-leucyl-phenylalanine-modified liposomes improve effects of C16-angiopoietin 1 in acute animal model of multiple sclerosis.","authors":"Xiao-Xiao Fu, Han Qu, Jing Wang, Hua-Ying Cai, Hong Jiang, Hao-Hao Chen, Shu Han","doi":"10.1080/10717544.2023.2241664","DOIUrl":"10.1080/10717544.2023.2241664","url":null,"abstract":"<p><p>Gradual loss of neuronal structure and function due to impaired blood-brain barrier (BBB) and neuroinflammation are important factors in multiple sclerosis (MS) progression. Our previous studies demonstrated that the C16 peptide and angiopoietin 1 (Ang-1) compound (C + A) could modulate inflammation and vascular protection in many models of MS. In this study, nanotechnology and a novel nanovector of the leukocyte chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) were used to examine the effects of C + A on MS. The acute experimental autoimmune encephalomyelitis (EAE) model of MS was established in Lewis rats. The C + A compounds were conjugated to control nano-carriers and fMLP-nano-carriers and administered to animals by intravenous injection. The neuropathological changes in the brain cortex and spinal cord were examined using multiple approaches. The stimulation of vascular injection sites was examined using rabbits. The results showed that all C + A compounds (C + A alone, nano-carrier C + A, and fMLP-nano-carrier C + A) reduced neuronal inflammation, axonal demyelination, gliosis, neuronal apoptosis, vascular leakage, and BBB impairment induced by EAE. In addition, the C + A compounds had minimal side effects on liver and kidney functions. Furthermore, the fMLP-nano-carrier C + A compound had better effects compared to C + A alone and the nano-carrier C + A. This study indicated that the fMLP-nano-carrier C + A could attenuate inflammation-related pathological changes in EAE and may be a potential therapeutic strategy for the treatment of MS and EAE.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2241664"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10323875","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 phospholipon®90H complex nanocarrier with enhanced oral bioavailability and anti-inflammatory potential of genistein.","authors":"Vaishnavi S Shete, Darshan R Telange, Nilesh M Mahajan, Anil M Pethe, Debarshi K Mahapatra","doi":"10.1080/10717544.2022.2162158","DOIUrl":"10.1080/10717544.2022.2162158","url":null,"abstract":"<p><p>Genistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon^®90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, <i>in vitro</i> dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon^®90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon^®90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon^®90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2162158"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10480462","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":"Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum.","authors":"Koyeli Girigoswami, Pragya Pallavi, Agnishwar Girigoswami","doi":"10.1080/10717544.2023.2284684","DOIUrl":"10.1080/10717544.2023.2284684","url":null,"abstract":"<p><p>It is evident that site-specific systemic drug delivery can reduce side effects, systemic toxicity, and minimal dosage requirements predominantly by delivering drugs to particular pathological sites, cells, and even subcellular structures. The endoplasmic reticulum (ER) and associated cell organelles play a vital role in several essential cellular functions and activities, such as the synthesis of lipids, steroids, membrane-associated proteins along with intracellular transport, signaling of Ca²⁺, and specific response to stress. Therefore, the dysfunction of ER is correlated with numerous diseases where cancer, neurodegenerative disorders, diabetes mellitus, hepatic disorder, etc., are very common. To achieve satisfactory therapeutic results in certain diseases, it is essential to engineer delivery systems that can effectively enter the cells and target ER. Nanoparticles are highly biocompatible, contain a variety of cargos or payloads, and can be modified in a pliable manner to achieve therapeutic effectiveness at the subcellular level when delivered to specific organelles. Passive targeting drug delivery vehicles, or active targeting drug delivery systems, reduce the nonselective accumulation of drugs while reducing side effects by modifying them with small molecular compounds, antibodies, polypeptides, or isolated bio-membranes. The targeting of ER and closely associated organelles in cells using nanoparticles, however, is still unsymmetrically understood. Therefore, here we summarized the pathophysiological prospect of ER stress, involvement of ER and mitochondrial response, disease related to ER dysfunctions, essential therapeutics, and nanoenabled modulation of their delivery to optimize therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2284684"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290680","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":"Polysialic acid-functionalized liposomes for efficient honokiol delivery to inhibit breast cancer growth and metastasis.","authors":"Xin Li, Shuang Guan, Henan Li, Dong Li, Dan Liu, Jing Wang, Wenquan Zhu, Guihua Xing, Liling Yue, Defu Cai, Qi Zhang","doi":"10.1080/10717544.2023.2181746","DOIUrl":"10.1080/10717544.2023.2181746","url":null,"abstract":"<p><p>To improve the anti-metastasis effects of honokiol (HNK) on breast cancer, we designed cationic liposomes (Lip) in which HNK was encapsulated into Lip, and its surface was modified with negatively charged polysialic acid (PSA-Lip-HNK) for efficient treatment of breast cancer. PSA-Lip-HNK possessed a homogeneous spherical shape and high encapsulation efficiency. <i>In vitro</i> 4T1 cell experiments indicated that PSA-Lip-HNK increased cellular uptake and cytotoxicity via the endocytosis pathway mediated by PSA and selectin receptors. Furthermore, the significant antitumor metastasis impact of PSA-Lip-HNK was confirmed by wound healing and cell migration and invasion. Enhanced <i>in vivo</i> tumor accumulation of the PSA-Lip-HNK was observed in 4T1 tumor-bearing mice by living fluorescence imaging. For <i>in vivo</i> antitumor experiments using 4T1 tumor-bearing mice, PSA-Lip-HNK exhibited a higher tumor growth and metastasis inhibition compared with unmodified liposomes. Therefore, we believe that PSA-Lip-HNK well combined biocompatible PSA nano-delivery and chemotherapy, providing a promising drug delivery approach for metastatic breast cancer therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2181746"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10753036","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":"Lipidization as a tool toward peptide therapeutics.","authors":"Aneta Myšková, David Sýkora, Jaroslav Kuneš, Lenka Maletínská","doi":"10.1080/10717544.2023.2284685","DOIUrl":"10.1080/10717544.2023.2284685","url":null,"abstract":"<p><p>Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2284685"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444273","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":"Oral delivery of nerolidol alleviates cyclophosphamide-induced renal inflammation, apoptosis, and fibrosis via modulation of NF-κB/cleaved caspase-3/TGF-β signaling molecules.","authors":"Ashif Iqubal, Abul Kalam Najmi, Shadab Md, Huda Mohammed Alkreathy, Javed Ali, Mansoor Ali Syed, Syed Ehtaishamul Haque","doi":"10.1080/10717544.2023.2241661","DOIUrl":"10.1080/10717544.2023.2241661","url":null,"abstract":"<p><p>Cyclophosphamide (CP) is one of the most extensively used antineoplastic drug, but the nephrotoxicity caused by this drug is a major limiting factor for its use. Nerolidol (NERO) is a natural bioactive compound with diverse pharmacological actions. <i>In Vitro</i> and <i>in vivo study</i> was performed using HK-2 renal cells and Swiss Albino mice. Cell lines and animals were treated with NERO 25 and 50 µM + 30 µM CP (<i>in vitro</i>), 200 and 400 mg/kg, p.o. NERO from day 1 to day 15 + 200 mg/kg, i.p. CP on day 17 as single intraperitoneal injection (<i>in vivo</i>). The makers of oxidative stress, renal-specific injury markers, inflammation, apoptosis, fibrosis, and histopathological changes were studied. The study's outcome showed a significant reduction in the level of malonaldehyde and interleukin-6 (p < 0.01), tumor necrosis factor-α, IL-1β (p < 0.001), and an increase in the superoxide dismutase, catalase, glutathione and interleukin-10 level (p < 0.01), in the <i>in vivo</i> study when treated with NERO 400 and compared with CP 200. <i>In Vitro</i> study showed reduced expression of nuclear factor kappa light chain enhancer of activated B cells, cleaved caspase-3, kidney injury molecule-1 and transforming growth factor-β-1 (p < 0.001), when treated with NERO 50 µM whereas NERO 25 µM only reduced the level of cleaved caspase-3 (p < 0.05) when compared with 30 µM. NERO 400 also reduced uric acid (p < 0.05), urea (p < 0.01), blood urea nitrogen, and serum creatinine levels (p < 0.001) and increased the level of blood-urea-nitrogen/creatinine ratio (p < 0.001). Additionally, the level of fibrosis-specific markers such as transforming growth factor-β1, hyaluronic acid (p < 0.01), 4-hydroxyproline, a collagen-rich area in Masson's' trichome stain, and Smad3 expression was also significantly reduced (p < 0.001). Furthermore, the outcome of multiple renal staining showed structural reversal aberrations, reduction of the thick basement membrane, and glycogen level toward normal when treated with NERO 400. Thus, the study showed a novel mechanistic modality of NERO against cyclophosphamide-induced renal toxicity. The outcome of this study can be considered a step closer to the development of an adjuvant to mitigate cyclophosphamide-induced renal toxicity among patients treated with cyclophosphamide.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2241661"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976145","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":"Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: statistical optimization and clinical assessment.","authors":"Heba Amin Elgendy, Amna M A Makky, Yara E Elakkad, Radwa M Ismail, Nihal Farid Younes","doi":"10.1080/10717544.2022.2162159","DOIUrl":"10.1080/10717544.2022.2162159","url":null,"abstract":"<p><p>Atorvastatin calcium (ATV) is a well-known anti-hyperlipidemic drug currently being recognized for possessing an anti-inflammatory effect. Introducing it as a novel remedy for periodontitis treatment necessitates developing a syringeable modified delivery system capable of targeting inflammation within the periodontal pockets. Thus, a 3³ Box-Behnken design was used to generate eugenol enriched PEGylated cubosomes. Based on the desirability function, the optimized formulation (OEEPC) was selected exhibiting a solubilization efficiency (SE%) of 97.71 ± 0.49%, particle size (PS) of 135.20 ± 1.11 nm, polydispersity index (PDI) of 0.09 ± 0.006, zeta potential (ZP) of -28.30 ± 1.84 mV and showing a sustained drug release over 12 h. It displayed a cubic structure under the transmission electron microscope, furthermore, it was stable upon storage for up to 30 days. Hence, it was loaded into an optimum syringeable in-situ gel (ISG) which displayed the desired periodontal gelation temperature (34 ± 0.70 °C) and an adequate gelation time (46 ± 2.82 sec), it also released approximately 75% of the drug within 72 h. Clinical evaluation of the ISG showed a promising percentage reduction of about 58.33% in probing depth, 90% in the bleeding index, 81.81% in the plaque index, and 70.21% in gingival levels of transforming growth factor-β1. This proved that the formulated syringeable intra-pocket delivery system of ATV is an efficient candidate for diminishing inflammation in periodontitis.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2162159"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9087721","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":"First-in-human study to assess the pharmacokinetics, tolerability, and safety of single-dose oxybutynin hydrochloride administered via a microprocessor-controlled intravaginal ring.","authors":"Willem de Laat, Lisa Pagan, R Karl Malcolm, Maarten Wiegerinck, Victor Nickolson, Bertine Huisman, Rik Stuurman, Michiel van Esdonk, Naomi Klarenbeek","doi":"10.1080/10717544.2023.2180113","DOIUrl":"10.1080/10717544.2023.2180113","url":null,"abstract":"<p><p>Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept <i>in situ</i> for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite <i>N</i>-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were <i>C</i>_max 5.4 ± 2.7 ng/mL, AUC_inf 34.9 ± 17.4 h ng/mL, <i>t</i>_1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were <i>C</i>_max 3.9 ± 2.5 ng/mL, AUC_inf 51.1 ± 43.1 h ng/mL, <i>t</i>_1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2180113"},"PeriodicalIF":6.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800808","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}