International Journal of Pharmaceutics最新文献

{"title":"Nanotechnology used for siRNA delivery for the treatment of neurodegenerative diseases: Focusing on Alzheimer’s disease and Parkinson’s disease","authors":"","doi":"10.1016/j.ijpharm.2024.124786","DOIUrl":"10.1016/j.ijpharm.2024.124786","url":null,"abstract":"<div><div>Neurodegenerative diseases (ND) are often accompanied by dementia, motor dysfunction, or disability. Caring for these patients imposes a significant psychological and financial burden on families. Until now, there are no effective methods for the treatment of NDs. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common. Recently, studies have revealed that the overexpression of certain genes may be linked to the occurrence of AD and PD. Small interfering RNAs (siRNAs) are a powerful tool for gene silencing because they can specifically bind to and cleave target mRNA. However, the intrinsic properties of naked siRNA and various physiological barriers limit the application of siRNA in the brain. Nanotechnology is a promising option for addressing these issues. Nanoparticles are not only able to protect siRNA from degradation but also have the advantage of crossing various physiological barriers to reach the brain target of siRNA. In this review, we aim to introduce diverse nanotechnology used for delivering siRNA to treat AD and PD. Finally, we will briefly discuss our perspectives on this promising field.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390484","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":"In-line porosity and hardness monitoring of tablets by means of optical coherence tomography","authors":"","doi":"10.1016/j.ijpharm.2024.124808","DOIUrl":"10.1016/j.ijpharm.2024.124808","url":null,"abstract":"<div><div>In-line monitoring of critical quality attributes (CQAs) during a tableting process is an essential step toward a real-time release strategy. Such CQAs can be the tablet mass, the API content, dissolution, hardness and tensile strength. Since dissolution testing is laborious and time-consuming and cannot be performed in-line, it is desirable to replace dissolution testing with predictive models based on other CQAs that affect the dissolution characteristics, such as the tablet porosity and hardness. Traditionally, porosity is determined offline via gas adsorption methods or other techniques, such as Terahertz spectroscopy or gas in scattering media absorption spectroscopy. Tablet hardness is typically established using a hardness tester. While these destructive tests can readily be performed at-line, they have limited applicability in in-line settings for a high-percentage inspection. Optical coherence tomography (OCT) has recently been proposed as a possible tool for determining quality attributes. This work describes the first application of OCT for the prediction of tablet porosity and hardness. OCT measurements of tablets produced in a ConsiGma 25™ tableting line and a Stylcam 200R compaction simulator in several compaction force settings were performed and correlated with the porosity and hardness. It was demonstrated that OCT can easily be installed in-line and provide real-time information about critical material attributes. These insights confirm the applicability of OCT as a real-time quality control tool and its potential to replace time-consuming and destructive offline measurements.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390471","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":"The effect of temperature-dependent drug viscosity on needle-free jet injection","authors":"","doi":"10.1016/j.ijpharm.2024.124777","DOIUrl":"10.1016/j.ijpharm.2024.124777","url":null,"abstract":"<div><div>Highly viscous drugs cannot be delivered through a needle. Typically, this means that these drugs are formulated at lower concentrations, demanding higher delivery volumes, which often must be delivered intravenously. Jet injection may provide an important solution for viscous drug delivery. Jet injection is a needle-free drug delivery technique whereby a liquid drug is formed into a hair-thin (∼200 µm) high-speed (&gt;100 m/s) jet that penetrates and delivers itself into tissue. While it may seem that it would be just as difficult to form a viscous drug into a high-speed jet as it is to force it down a needle, this is not the case. Recent work has revealed that ‘viscous-heating’ during jet injection can result in significant temperature increase, and resultant viscosity decrease, in a thin outer-layer of the jet; this phenomenon effectively results in the drug ‘self-lubricating’ as it passes through a jet injection orifice. Despite the potential for this finding to revolutionise the subcutaneous delivery of high-viscosity drugs, little further work in this area has since been reported on. In this work we develop finite element models of needle-free injection to investigate how viscous heating affects jet production, how heat exchange with the orifice material influences this process, and to what extent jet production is affected by the initial temperature of the fluid. We then conduct novel high-speed measurements of jet and orifice temperature changes due to viscous heating. We find that viscous heating is responsible for approximately doubling the speed of jets that can be produced with very viscous fluid (1 Pa·s) at room temperature. The thermal conductivity of the orifice can transfer heat away from the perimeter of the jet, and thus reduce the lubricating effect of viscous heating. We then show that by preheating 99 % glycerol (1 Pa·s) from 7 °C to 37 °C the jet speed can be increased 6-fold. We also demonstrate the successful delivery of a very viscous glycerol solution using preheated jet injection into ex vivo porcine tissue. Given that 99 % glycerol is 10- to 100-fold more viscous than current protein therapeutics, our findings demonstrate the potential for jet injection, with or without additional drug preheating, to deliver drug formulations, needle-free, that are much more viscous than those currently delivered through needles.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380829","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":"Effects of nanoparticle size, shape, and zeta potential on drug delivery","authors":"","doi":"10.1016/j.ijpharm.2024.124799","DOIUrl":"10.1016/j.ijpharm.2024.124799","url":null,"abstract":"<div><div>Nanotechnology has brought about a significant revolution in drug delivery, and research in this domain is increasingly focusing on understanding the role of nanoparticle (NP) characteristics in drug delivery efficiency. First and foremost, we center our attention on the size of nanoparticles. Studies have indicated that NP size significantly influences factors such as circulation time, targeting capabilities, and cellular uptake. Secondly, we examine the significance of nanoparticle shape. Various studies suggest that NPs of different shapes affect cellular uptake mechanisms and offer potential advantages in directing drug delivery. For instance, cylindrical or needle-like NPs may facilitate better cellular uptake compared to spherical NPs. Lastly, we address the importance of nanoparticle charge. Zeta potential can impact the targeting and cellular uptake of NPs. Positively charged NPs may be better absorbed by negatively charged cells, whereas negatively charged NPs might perform more effectively in positively charged cells. This review provides essential insights into understanding the role of nanoparticles in drug delivery. The properties of nanoparticles, including size, shape, and charge, should be taken into consideration in the rational design of drug delivery systems, as optimizing these characteristics can contribute to more efficient targeting of drugs to the desired tissues. Thus, research into nanoparticle properties will continue to play a crucial role in the future of drug delivery.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380828","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":"Nanosystems for targeted drug Delivery: Innovations and challenges in overcoming the Blood-Brain barrier for neurodegenerative disease and cancer therapy","authors":"","doi":"10.1016/j.ijpharm.2024.124800","DOIUrl":"10.1016/j.ijpharm.2024.124800","url":null,"abstract":"<div><div>The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood–brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB’s regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390483","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 finasteride patch for the treatment of androgenetic alopecia: A study of promoting permeability strategy using synthetic novel O-acylmenthols combined with ion-pair","authors":"","doi":"10.1016/j.ijpharm.2024.124802","DOIUrl":"10.1016/j.ijpharm.2024.124802","url":null,"abstract":"<div><div>Currently, finasteride (FIN) is approved to treat androgenetic alopecia only orally, and the application of FIN in transdermal drug delivery system (TDDS) has introduced a new approach for treating the disease. This study was aimed to develop a FIN transdermal patch for the treatment of androgenetic alopecia（AGA） by combing ion-pair and O-acylmenthols (AM) as chemical permeation enhancers (CPEs). The formulation of patch was optimized though single-factor investigation and Box-Behnken design. The pharmacokinetics and androgenetic alopecia pharmacodynamics of the patch were evaluated. Additionally, the permeability enhancement mechanisms of ion-pair and AMs were explored at both the patch and skin levels. The effects of ion-pair and AMs on the patch were characterized by rheology study, FTIR, and molecular docking, and the effects on the skin were assessed through ATR-FTIR, Raman study, DSC, CLSM and molecular dynamics. The finalized formulation of FIN patches was consisted of 5 % (<em>w</em>/<em>w</em>) synthetic FIN-CA (Citric Acid), 6 % MT-C6 as CPEs, 25-AAOH as a pressure-sensitive adhesive (PSA), with a patch thickness of 80 ± 5 μm. The final <em>Q</em>_{24 h} is 78.22 ± 5.18 μg/cm². Based on the high FIN permeability, the pharmacokinetic analysis revealed that the FIN patch group exhibited a slower absorption rate (<em>t</em>_max = 7.3 ± 2.7 h), lower peak plasma concentration and slower metabolic rate (<em>t</em>_1/2 = 6.2 ± 0.8 h, <em>MRT</em>_0-t = 26.0 ± 7.8 h) compared to the oral group. Moreover, the FIN patch also demonstrated the same effect as the oral group in promoting hair growth in AGA mice. The results indicated that both FIN-CA and AMs could enhance the fluidity of the PSA and weaken the interaction between FIN-CA and PSA, thereby promoting the release of the FIN from the patch. The interaction sites on the skin for ion-pair and the four AMs were found in the stratum corneum (SC) of the skin, disrupting the tight arrangement of stratum corneum lipids. This study serves as a reference for the multi-pathway administration of FIN and the combination of ion-pair with AMs to enhance drug permeation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377795","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":"Novel natural lipids based NLC containing finasteride improved androgenetic alopecia treatment in rats","authors":"","doi":"10.1016/j.ijpharm.2024.124804","DOIUrl":"10.1016/j.ijpharm.2024.124804","url":null,"abstract":"<div><div>Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting millions of men and women worldwide. Current formulations used to treat this condition often lead to a wide variety of side effects, ranging from allergies to sexual disfunction, especially when those drugs are administered orally. In this study, we developed and tested unique formulations containing nanostructured lipid carriers (NLC) composed of lipids extracted from fruit seeds, carrying finasteride to enhance efficacy of AGA treatment. By stabilizing the hydrophobic compounds in the solid matrix, three formulations of NLC were engineered and successfully prepared. Further an <em>in vivo</em> model of AGA was induced in rats by the administration of testosterone, as a platform to evaluate the efficiency of the formulations. The chosen formulation exhibited high bioavailability, medium size of 124.5 nm and PdI of 0.143, without systemic absorption. In addition, it promoted efficient and significant follicle restoration in AGA induced rats by increasing number of active bulbs and showed to be a safe formulation for topical application. The results of this research indicate that the presented formulation has significant potential to yield improved outcomes in AGA treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377799","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":"Novel sodium tauroursodeoxycholate-based multifunctional liposomal delivery system for encapsulation of oleanolic acid and combination therapy of type 2 diabetes mellitus","authors":"","doi":"10.1016/j.ijpharm.2024.124803","DOIUrl":"10.1016/j.ijpharm.2024.124803","url":null,"abstract":"<div><div>Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377800","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":"Bacterial ghosts engineered with lipidated antigens as an adjuvant-free vaccine for Chlamydia abortus","authors":"","doi":"10.1016/j.ijpharm.2024.124801","DOIUrl":"10.1016/j.ijpharm.2024.124801","url":null,"abstract":"<div><div>Bacterial ghosts (BGs) provide novel vaccine delivery platforms because of their inherent adjuvant properties and efficient antigen delivery capabilities. However, effective engineering strategies are required to modify them for different antigens. In this study, the <em>Escherichia coli</em> (<em>E. coli</em>) ghost was modified by using a lpp’-ompA chimera, a widely used bacterial surface display vector, with a protective antigen macrophage infectivity potentiator (MIP) of <em>Chlamydia abortus</em> (<em>C. abortus</em>), and its protective effect was evaluated in a mouse model. The MIP fusion protein accumulated at 1.2% of the ghost total protein mass and a significant portion of the protein was modified into lipoproteins upon translocation to the BG surface. Lipidated MIP-modified recombinant <em>E. coli</em> ghosts (rECG-lpp’-MIP) effectively promoted antigen-presenting cells (APCs) uptake of antigens and stimulated APCs activation <em>in vivo</em> and <em>in vitro</em>. Immunization with rECG-lpp’-MIP and no adjuvant induced intense specific humoral responses as well as Th1-biased cellular immune responses, which significantly improved the efficiency of <em>C. abortus</em> infection clearance in mice and reduced pathological damage to the uterus. In summary, this study demonstrates that recombinant <em>E. coli</em> ghosts modified with lipidated antigens could help to develop an effective <em>C. abortus</em> vaccine and aid in the development of a universal adjuvant-free vaccine platform.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377796","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":"The molecular design of novel phospholipid-inspired ionic liquid transdermal penetration enhancers: Innovative insights on the action mode and mechanism","authors":"","doi":"10.1016/j.ijpharm.2024.124805","DOIUrl":"10.1016/j.ijpharm.2024.124805","url":null,"abstract":"<div><div>Ionic liquid transdermal penetration enhancers (IL@TPEs) as new enhancement methods have significant advantages in the transdermal drug delivery system. However, the scientific frameworks for the design of efficient IL@TPEs and their applications in transdermal formulations were still lack. So, a series of novel biomimetic phospholipid-inspired IL@TPEs (PIL@TPEs) were designed and synthesized. The developed QSARs proved that enhancement efficacy of PIL@TPEs depended on p<em>K</em>a of drugs and M.W., Polar., and p<em>K</em>a of cations. Surprisingly, the PIL@TPEs dissociated during transdermal process, and skin penetration amounts of acidic drugs was inversely proportional to skin retention amounts of cations, which showed that action modes of PIL@TPEs were different from conventional enhancers. The novel mechanisms of PIL@TPEs were elucidated by quantitative determination of dynamic interaction among cations, anions, drugs, and skins. The PIL@TPEs with high enhancement efficiency owned strong interactions with drugs determined by ATR-FTIR, Raman and NOESY. Moreover, the PIL@TPEs owning better stability in skin ensured the production of strong interactions with lipids and keratins characterized by ATR-FTIR, ¹H NMR and CLSM. The good safety of optimized PIL@TPEs was proved by determining cytotoxicity, apoptosis, inflammatory cells, and cytokines. In conclusion, this project will make an important contribution to the design and application of IL@TPEs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380830","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}