Drug Development and Industrial Pharmacy最新文献

{"title":"Pyroligneous extract, a biomaterial derived from pyrolytic palm kernel shell wood vinegar, as a novel diabetic wound healing aid: An animal study.","authors":"Yongyuth Theapparat, Sunisa Khongthong, Natthrit Roekngam, Tan Suwandecha, Jongdee Nopparat, Damrongsak Faroongsarng","doi":"10.1080/03639045.2024.2427795","DOIUrl":"https://doi.org/10.1080/03639045.2024.2427795","url":null,"abstract":"<p><strong>Objective: </strong>Wound in diabetes is difficult to heal since it possesses excessive inflammation. The aim of the study was to evaluate wound healing activity of chitosan-based hydrogel containing pyroligneous acid in diabetic animals.</p><p><strong>Significance: </strong>Pyroligneous acid, a byproduct of biochar production from palm kernel shell biomass, contained oxygenated compounds which, with extracting enrichment, could promote wound healing.</p><p><strong>Methods: </strong>Streptozotocin-induced diabetic male jcl: ICR mice were subjected to create wounds and treat with hydrogel containing pyroligneous extract at dose strengths of 0 (placebo), 100 and 150 μg/g-gel. Commercial gel (Intrasite®) was used as an active comparator. On 3-, 7-, 10- and 14-day post wounding, wound contraction was rated and wound site tissues were collected. The specimens were H&E stained and microscopically examined to evaluate histological responses. The underline wound healing related cytokine and polypeptide expressions were determined using real-time PCR and western blot.</p><p><strong>Results: </strong>It was found that the extract accelerated the healing process in a dose-dependent manner where at dose strength of 150 μg/g-gel was as effective as active comparator. It increased gene expression of the cytokine and related proteins in TGF-β/SMAD signaling pathway and may further activate diabetic induced TGF-β downregulation to restore up to the level that healthy skin tissues express. It also enhanced the expressions of Akt, FAK, RhoA and Rac-1 and evidently activated phosphorylation of Akt and FAK.</p><p><strong>Conclusion: </strong>The study demonstrated the extract could be a novel biomaterial for healing of such a chronic inflammatory wound as the wound in diabetes.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and characterization of soluplus-based nanosuspension for dissolution enhancement of indomethacin using ultrasonic assisted precipitation method for formulation and Box-Behnken design for optimization.","authors":"Areen Alshweiat, Eqbal Abu-Alkebash, Alaa Abuawad, Tamara Athamneh, Shorooq Abukhamees, Muna Oqal","doi":"10.1080/03639045.2024.2424307","DOIUrl":"10.1080/03639045.2024.2424307","url":null,"abstract":"<p><strong>Objectives: </strong>Nanosuspensions are increasingly recognized as a valuable technology for enhancing poorly water-soluble drugs' solubility and dissolution rate, thereby improving their bioavailability. In this study, we employed ultrasonic-assisted precipitation to fabricate nanosuspensions of indomethacin (IND), utilizing Soluplus^® (Sol) as a stabilizing agent. Our objectives were driven by hypotheses centered on optimizing formulation variables and developing predictive models for optimal IND formulations.</p><p><strong>Significance: </strong>This research highlights the Box-Behnken design (BBD) as a powerful tool that optimizes the properties of IND nanosuspensions, thus significantly enhancing their dissolution rate.</p><p><strong>Methods: </strong>The impacts of the independent variables on the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were investigated using BBD. The optimized nanosuspension was freeze-dried with 3% trehalose to produce a dry nanosuspension (DNS). The DNS was characterized by SEM, DSC, XRPD, solubility, and dissolution.</p><p><strong>Results: </strong>The IND: Sol ratio and sonication power significantly affected the MPS and ZP of the nanosuspensions. The optimized formulation showed MPS, PDI, and ZP of 144.77 ± 6.68 nm, 0.26 ± 0.08, and -24.6 ± 1.90 mV, respectively. The DNS exhibited spherical particle morphology. The DSC and XRPD confirmed the amorphous state of IND with enhanced solubility and dissolution of IND. DNS showed a 3.7-fold increase in drug release in the first 15 min compared with raw IND.</p><p><strong>Conclusions: </strong>This study demonstrated the critical role of BBD in accurately predicting the values of independent variables essential for formulating optimal nanosuspensions. These formulations possess specific properties that can be effectively integrated into various dosage forms tailored for different routes of administration.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, Characterization and Evaluation of Minocycline Hydrochloride Loaded Polyurethane/Collagen Nanofibers via Electrospinning as Wound Dressings.","authors":"Tuğba Eren Böncü, Çiğdem Yücel, Ahmet Ceylan, Mehmet Çadir, Ertuğrul Şahmetlioğlu","doi":"10.1080/03639045.2024.2426581","DOIUrl":"https://doi.org/10.1080/03639045.2024.2426581","url":null,"abstract":"<p><p><b>Objective</b> It was aimed to formulate minocyline.HCI loaded electrospun polyurethane/collagen (PU/Col) and polyurethane/collagen/polycaprolactone (PU/Col/PCL) nanofibers are intended for use as a wound dressing. <b>Methods:</b>The effect of polymer ratio and addition of PCL on the morphology, diameter, drug delivery, encapsulation efficiency, mechanical properties, antibacterial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, cytotoxicity, cell adhesion and proliferation were investigated. 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the cytotoxicity of the nanofibers on the human dermal fibroblast (HDF) cell line. Cell proliferation/adhesion was also determined by imaging HDF cells seeded on mats with scanning electron microscopy/fluorescence microscopy. <b>Results:</b>All nanofibers were bead-free and smooth in the diameter range of 866.7-882.4 nm. They had favorable encapsulation efficiency (≥79.3%), controlled drug release up to 24 hours and did not have cytotoxic effects. Although collagen was preferred for cell adhesion and proliferation, its spinnability and mechanical properties were poor. While PU improved the spinnability of collagen, its mechanical properties also enhanced with the addition of PCL. Nevertheles, all mats led to favorable cell adhesion and proliferation. All the nanofibers had antimicrobial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. <b>Conclusion:</b>In conclusion, PU/Col and PU/Col/PCL nanofiber mats, which had favorable encapsulation efficiency, controlled drug release and antibacterial activity at least 24 hours, cell viability, proliferation, adhesion, mechanical properties to be used as wound dressing, were successfully prepared.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH sensitive lipid polymeric hybrid nanoparticle (LPHNP) of paclitaxel and curcumin for targeted delivery in breast cancer.","authors":"Hrishikesh Sarma, Ankit Dutta, Alakesh Bharali, Sheikh Sofiur Rahman, Sunayana Baruah, Nikhil Biswas, Bhanu P Sahu","doi":"10.1080/03639045.2024.2421198","DOIUrl":"10.1080/03639045.2024.2421198","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer.</p><p><strong>Significance: </strong>Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile.</p><p><strong>Methods: </strong>Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology.</p><p><strong>Results: </strong>LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. <i>In vitro</i> release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC₅₀ value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. <i>In vivo</i> pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX.</p><p><p>The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferric ions crosslinked hyaluronic acid beads: potentials for drug delivery use.","authors":"Hadeia Mashaqbeh, Rana Obaidat, Meriem Rezigue, Derar Omari, Ghyda'a Shakhatreh","doi":"10.1080/03639045.2024.2422497","DOIUrl":"10.1080/03639045.2024.2422497","url":null,"abstract":"<p><strong>Introduction and purpose: </strong>Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads.</p><p><strong>Methods: </strong>The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead's morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and <i>in vitro</i>, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated.</p><p><strong>Results: </strong>The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The <i>in vitro</i> drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model.</p><p><strong>Conclusions: </strong>This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of cocoa butter for formulation of fast melt tablets containing memantine hydrochloride.","authors":"Ying Hui Loke, Hiu Ching Phang, Ganesan Gobal, Palanirajan Vijayaraj Kumar, Phei Er Kee, Riyanto Teguh Widodo, Bey Hing Goh, Kai Bin Liew","doi":"10.1080/03639045.2024.2417999","DOIUrl":"https://doi.org/10.1080/03639045.2024.2417999","url":null,"abstract":"<p><strong>Introduction: </strong>Fast melt tablets (FMTs) provide a convenient dosage form that rapidly dissolves on the tongue without the need for water. Cocoa butter serves as a suitable matrix system for FMTs formulation, facilitating rapid disintegration at body temperature.</p><p><strong>Objectives: </strong>This study aimed to formulate FMTs using cocoa butter as a base and investigate the effect of various disintegrants and superdisintegrants on their characteristics.</p><p><strong>Methods: </strong>Cocoa butter-based FMTs were prepared <i>via</i> the fusion molding technique. Different disintegrants and superdisintegrants were added at varying concentrations and subjected to characterization. The optimal formulation was selected and incorporated with 10 mg memantine hydrochloride.</p><p><strong>Results: </strong>The optimal FMT formulation consisted of 340 mg cocoa butter, 75 mg starch, and 75 mg crospovidone, exhibiting a hardness of 17.12 ± 0.31 N and a disintegration time of 32.67 ± 0.17 s. Furthermore, FMTs demonstrated a faster release profile compared to the commercially available product, Ebixa. SEM micrographs revealed homogenous blending of individual ingredients within the cocoa butter matrix and FT-IR analysis confirmed the chemical stability of memantine hydrochloride in the formulation. The dissolution profile of F17 suggested that the drug in FMTs released faster compared to Ebixia. Memantine hydrochloride achieved 98.07% of drug release in FMTs at 10 min. Moreover, the prepared FMTs exhibited stability for at least 6 months.</p><p><strong>Conclusion: </strong>The successful development of cocoa butter-based FMTs containing memantine hydrochloride highlights the potential of cocoa butter as viable alternative matrix-forming material for FMTs production. This innovative formulation offers patients a convenient alternative for medication administration.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphatic targeting of cilnidipine by designing and developing a nanostructured lipid carrier drug delivery system.","authors":"Preeti Rajabhau Meshram, Nisharani Sudhakar Ranpise","doi":"10.1080/03639045.2024.2415638","DOIUrl":"https://doi.org/10.1080/03639045.2024.2415638","url":null,"abstract":"<p><strong>Objective: </strong>The objective of current research is to design, develop, and optimize a cilnidipine (CLN) nanostructured lipid carrier (NLC)-based drug delivery system for the effective treatment of hypertension (HT).</p><p><strong>Significance: </strong>Oral administration of CLN-loaded NLC (CLN NLC) containing glyceryl monostearate (GMS) as a solid and isopropyl myristate (IPM) as a liquid lipid may show remarkable lymphatic uptake through payer patches.</p><p><strong>Methods: </strong>The emulsification probe sonication technique was used followed by optimization using 3² factorial designs.</p><p><strong>Results: </strong>The optimized batch showed a mean particle size of 115.4 ± 0.22 nm with encapsulation efficiency of 98.32 ± 0.23%, polydispersity index (PDI) of 0.342 ± 0.03, and zeta potential (ZP, <i>ζ</i>) was -60.5 ± 0.24 which indicate excellent physical stability. <i>In vitro</i> studies showed a controlled release of CLN NLCs. Pharmacokinetics studies determined the <i>C</i>_max of NLCs (373.47 ± 15.1) indicates 2.3-fold enhancement compared with plain drug (160.64 ± 7.63). Pharmacodynamic studies indicated that CLN NLCs were maintaining systolic blood pressure in a controlled manner without any signs of side effects.</p><p><strong>Conclusion: </strong>CLN NLCs significantly improved lymphatic delivery and proved to be effective in the treatment and management of HT. It has been proved that CLN NLCs are found to be better than any traditional CLN dosage form due to enhancement in solubility, absorption, bioavailability, intestinal permeability, avoidance of first-pass metabolism, P-glycoprotein efflux and reduction in dose-related side effects, achievement of controlled and sustained release action.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate.","authors":"Hiu Ching Phang, Zhi Qi Ng, Najwa Mohamad, Yik Ling Chew, Ashok Balaraman, Phei Er Kee, Kenji Mishima, Bey Hing Goh, Long Chiau Ming, Kai Bin Liew","doi":"10.1080/03639045.2024.2409168","DOIUrl":"https://doi.org/10.1080/03639045.2024.2409168","url":null,"abstract":"<p><strong>Background: </strong>Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset.</p><p><strong>Objective: </strong>This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films.</p><p><strong>Methods: </strong>Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterization tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young's modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behavior, accelerated stability, X-ray diffraction (XRD), and palatability.</p><p><strong>Results: </strong>FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 s), high flexibility (folding endurance > 300 times) and lower Young's modulus (1.308 ± 0.214).</p><p><strong>Conclusion: </strong>Oven drying method has been proven to be favorable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olive oil and flaxseed oil incorporating niosomes for enhanced <i>in vivo</i> anti-diabetic efficacy of canagliflozin.","authors":"Ghada Saad, Gamal M El Maghraby, Amal A Sultan","doi":"10.1080/03639045.2024.2409167","DOIUrl":"https://doi.org/10.1080/03639045.2024.2409167","url":null,"abstract":"<p><strong>Background: </strong>Canagliflozin (CFZ) is broadly implicated for the management of type 2 diabetes mellitus. Unfortunately, it has low oral bioavailability due to poor solubility behavior and restricted membrane permeability.</p><p><strong>Objective: </strong>The current work focuses on development of CFZ encapsulated niosomes for enhanced oral anti-diabetic efficacy.</p><p><strong>Methodology: </strong>Niosomes comprising Span 60 and cholesterol were formulated both in absence and presence of olive oil or flaxseed oil. These were evaluated <i>in vitro</i> for average vesicular size, structural morphology, CFZ entrapment efficiency, and drug release. Additionally, the oral hypoglycemic effect of CFZ encapsulated niosomes was explored in diabetic rats.</p><p><strong>Results: </strong>The fabricated niosomes were negatively charged spherical vesicles with a size range of 103.0-141.7 nm. These entrapped CFZ with efficiency ranging from 92.3% to 96.0%. Drug release investigations reflected that incorporating CFZ into niosomes significantly sustained drug release compared to the aqueous drug dispersion. Oral administration of niosomal formulations significantly enhanced the oral antidiabetic effect of CFZ. Comparing the tested niosomes, similar efficiency was shown eliminating the effect of composition.</p><p><strong>Conclusion: </strong>The enhanced oral bioavailability of niosomes' encapsulated drugs is related to niosomal vesicular structure which allows intact niosomes absorption. The study presented niosomes as promising carriers for improved oral anti-diabetic activity of CFZ.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β1 and FOXM1 siRNA co-loaded nanoparticles by Disulfide crosslinked PEG-PDMAEMA for the treatment of triple negative breast cancer and its bone metastases in vitro.","authors":"Xingbo Wang,Hong Huang,Wenxiu Xu,Yanling Gong,Songbo Shi,Xu Wan,Li Pengbiao","doi":"10.1080/03639045.2024.2404979","DOIUrl":"https://doi.org/10.1080/03639045.2024.2404979","url":null,"abstract":"INTRODUCTIONTriple negative breast cancer (TNBC) is characterized with higher malignancy and mortality and is prone to distant metastasis, among which bone is the most common site. It's urgent to explore new strategies for treatment of TNBC and its bone metastases.METHODSA tumor environment responsive vector, poly-(dimethylaminoethyl methacrylate)-SS-poly(ethylene glycol)-SS-poly-(dimethylaminoethyl methacrylate) (PDMAEMA-SS-PEG-SS-PDMAEMA), was constructed to co-delivery transforming growth factor-β1 (TGF-β1) siRNA and forkhead box M1 (FOXM1) siRNA in MDA-MB-231 cells. The preparation, characterization, in vitro release, stability, and transfection efficiency of nanoparticles were measured. Cell viability, migration and invasion of MDA-MB-231 cells were determined. Cell chemotactic migration and cell heterogeneity adhesion of MDA-MB-231 cells to the human osteoblast-like cell line MG-63 were determined.RESULTSPDMAEMA-SS-PEG-SS-PDMAEMA self assembled with siRNA at N/P of 15:1 into nanoparticles with particle size of 122 nm. In vitro release exhibited redox and pH sensitivity, and the nanoparticles protected siRNA from degradation by RNase and serum protein, remaining stable at 4 °C with similar transfection efficiency with lipo2000. Nanoparticles co-loaded with TGF-β1 siRNA and FOXM1 siRNA inhibited the cell viability, migration and invasion of MDA-MB-231 cells, as well as chemotactic migration and heterogeneous adhesion of MDA-MB-231 cells to MG-63 cells, showing a synergetic effect. After gene silencing on TGF-β1 and FOXM1, the epithelial to mesenchymal transition (EMT) related molecules vimentin mRNA expression decreased while E-cadherin increased.CONCLUSIONPDMAEMA-SS-PEG-SS-PDMAEMA was suitable for TGF-β1 siRNA and FOXM1 siRNA delivery, exhibiting synergetic inhibition effect on TNBC and its bone metastases, which might be related to its synergetic inhibition on EMT.","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}