Drug Delivery最新文献

{"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}

{"title":"Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, <i>in-vitro</i>, <i>in silico</i>, and <i>in-vivo</i> study.","authors":"Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh","doi":"10.1080/10717544.2023.2241665","DOIUrl":"10.1080/10717544.2023.2241665","url":null,"abstract":"<p><p>Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the <i>in-vivo</i> study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"30 1","pages":"2241665"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301848","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":"Statement of Retraction","authors":"","doi":"10.1353/pgn.2022.0083","DOIUrl":"https://doi.org/10.1353/pgn.2022.0083","url":null,"abstract":"","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2632 - 2632"},"PeriodicalIF":6.0,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45276664","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 novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer.","authors":"Xiaoming Cui,&nbsp;Fang Zhang,&nbsp;Yanyan Zhao,&nbsp;Pan Li,&nbsp;Ting Wang,&nbsp;Zhilu Xu,&nbsp;Jingjing Zhang,&nbsp;Weifen Zhang","doi":"10.1080/10717544.2022.2120567","DOIUrl":"https://doi.org/10.1080/10717544.2022.2120567","url":null,"abstract":"<p><p>Chemotherapy is the first choice for the treatment of cancer but it is still limited by insufficient kill efficiency and drug resistance. These problems urgently need to be overcome in a way that minimizes damage to the body. In this study, we designed the nanocomposite microparticles (NMPs) modified by cetuximab (Cet) and loaded anti-tumor agents- quercetin (QUE) and paclitaxel (PTX)- for eliciting specific drugs homing and enhancing the killing efficiency of chemotherapy drugs (P/Q@CNMPs). Physicochemical characteristics results presented that P/Q@CNMPs have a suitable aerodynamic diameter and uniform morphology that could meet the requirements of particles deposition in the lung. And it also had the characteristics of sustained-release and pH-responsive which could release the agents in the right place and has a continuous effect. <i>In vitro</i> and <i>in vivo</i> analysis results presented that P/Q@CNMPs have the accuracy targeting ability and killing effect on non-small cell lung cancer (NSCLC) which express positive epidermal growth factor receptor (EGFR) on the membrane. Furthermore, this system also has low toxicity and good biocompatibility. These results demonstrated that P/Q@CNMPs could be a potential intelligent targeting strategy used for chemo-resistant NSCLC therapies.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3123-3133"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547288","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":"Fabrication of bio-engineered chitosan nanoformulations to inhibition of bacterial infection and to improve therapeutic potential of intestinal microflora, intestinal morphology, and immune response in infection induced rat model.","authors":"Xiao Wan,&nbsp;Liu Liu,&nbsp;Lu Ding,&nbsp;Zhiqiang Zhu","doi":"10.1080/10717544.2022.2081381","DOIUrl":"https://doi.org/10.1080/10717544.2022.2081381","url":null,"abstract":"<p><p>Overdosage of antibiotics used to prevent bacterial infections in the human and animal gastrointestinal tract would result in disturbing of intestinal barrier, significant misbalancing effects of intestinal microflora and persuading bacterial resistance. The main objective of the present investigation is to design and develop novel combinations of organic curcumin (Cur) and antimicrobial peptide (Amp) loaded chitosan nanoformulations (Cur/Amp@CS NPs) to improve significant effects on antibacterial action, immune response, intestine morphology, and intentional microflora. The antibacterial efficiency of the prepared nanoformulations was evaluated using <i>Escherichia coli</i> (<i>E. coli</i>) induced bacterial infections in GUT of Rat models. Further, we studied the cytocompatibility, inflammatory responses, α-diversity, intestinal morphology, and immune responses of treated nanoformulations in rat GUT models. The results indicated that Cur/Amp@CS NPs are greatly beneficial for intestinal microflora and could be a prodigious alternative of antibiotics.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2002-2016"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498670","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":"Increased brain uptake of pterostilbene loaded folate modified micellar delivery system.","authors":"Yinan Wang,&nbsp;Yanan Su,&nbsp;Yunqiao Yang,&nbsp;Huan Jin,&nbsp;Moli Wu,&nbsp;Qian Wang,&nbsp;Pengyuan Sun,&nbsp;Jianbin Zhang,&nbsp;Xiaobo Yang,&nbsp;Xiaohong Shu","doi":"10.1080/10717544.2022.2126559","DOIUrl":"https://doi.org/10.1080/10717544.2022.2126559","url":null,"abstract":"<p><p>Effective chemotherapy for clinical treatment of brain diseases is still lacking due to the poor penetration of the blood-brain barrier (BBB). The aim of this study was to construct a folate modified pterostilbene (Pt) loaded polymeric micellar delivery system (F-Pt/M) with mPEG-PCL as carrier material to aim at penetrating the BBB for brain tissue targeting via receptor-mediated endocytosis. In this study, F-Pt/M was prepared using thin-film hydration method and then optimized by response surface methodology (RSM) with the entrapment efficiency (EE), drug loading (DL) and hydrodynamic diameter (HD) as indexes. The average hydrodynamic diameter and zeta potential of optimal F-Pt/M were 133.2 nm and 24.6 mV, respectively. DL (18.3%) and EE (98.6%) made the solubility of Pt in water about 25 times higher than that of crude Pt. Results of DSC evaluation revealed that drugs were successfully encapsulated inside the polymeric micelles. TEM images showed that homogeneous spherical micellar structures with a narrow size distribution were developed. The release result in vitro showed that F-Pt/M presented sustained release behavior compared to control free Pt solution. Compared to non-targeted Pt/M, F-Pt/M had a significantly higher cytotoxicity against FR-overexpressing A172 cells. In vitro cellular uptake tests illustrated that the micellar delivery system could significantly improve the accumulation of drugs in target cells via receptor-mediated endocytosis. BBB penetration value (P) of F-Pt/M was about 4 folds higher than that of free Pt group. In addition, drug targeting index (DTI) was calculated to determine targeting of F-Pt/M to the brain which was found to be 4.89, implying improved brain targeting was achieved. Hence, the developed F-Pt/M exhibited great potential for delivering more drug molecules across the BBB for the treatment of brain diseases.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3071-3086"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10544911","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":"Optimization of process parameters for fabrication of electrospun nanofibers containing neomycin sulfate and <i>Malva sylvestris</i> extract for a better diabetic wound healing.","authors":"Mohammed Monirul Islam,&nbsp;Varshini Hemmanahalli Ramesh,&nbsp;Penmetsa Durga Bhavani,&nbsp;Prakash S Goudanavar,&nbsp;N Raghavendra Naveen,&nbsp;B Ramesh,&nbsp;Santosh Fattepur,&nbsp;Predeepkumar Narayanappa Shiroorkar,&nbsp;Mohammed Habeebuddin,&nbsp;Girish Meravanige,&nbsp;Mallikarjun Telsang,&nbsp;Nagaraja Sreeharsha","doi":"10.1080/10717544.2022.2144963","DOIUrl":"https://doi.org/10.1080/10717544.2022.2144963","url":null,"abstract":"<p><p>Diabetes mellitus is one of the most concerning conditions, and its chronic consequences are almost always accompanied by infection, oxidative stress, and inflammation. Reducing excessive reactive oxygen species and the wound's inflammatory response is a necessary treatment during the acute inflammatory phase of diabetic wound healing. <i>Malva sylvestris</i> extract (MS) containing nanofibers containing neomycin sulfate (NS) were synthesized for this investigation, and their impact on the healing process of diabetic wounds was assessed. Using Design Expert, the electrospinning process for the fabrication of NS nanofibers (NS-NF) was adjusted for applied voltage (<i>X</i>₁), the distance between the needle's tip and the collector (<i>X</i>₂), and the feed rate (<i>X</i>₃) for attaining desired entrapment efficacy [EE] and average nanofiber diameter (ND). The optimal formulation can be prepared with 19.11 kV of voltage, 20 cm of distance, and a flow rate of 0.502 mL/h utilizing the desirability approach. All the selected parameters and responses have their impact on drug delivery from nanofibers. In addition, <i>M. sylvestris</i> extracts have been added into the optimal formulation [MS-NS-NF] and assessed for their surface morphology, tensile strength, water absorption potential, and in vitro drug release studies. The NS and MS delivery from MS-NS-NF has been extended for more than 60 h. <i>M. sylvestris</i>-loaded nanofibers demonstrated superior antibacterial activity compared to plain NS nanofibers. The scaffolds featured a broad aspect and a highly linked porous fibrous network structure. Histomorphometry study and the in vitro scratch assay demonstrate the formulation's efficacy in treating diabetic wound healing. The cells treated with MS-NS-NF in vivo demonstrated that wound dressings successfully reduced both acute and chronic inflammations. To improve the healing of diabetic wounds, MS-NS-NF may be regarded as an appropriate candidate for wound dressing.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3370-3383"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10545892","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":"Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment.","authors":"Xiangming Kong, Miao Feng, Lihuang Wu, Yiyan He, Hongli Mao, Zhongwei Gu","doi":"10.1080/10717544.2022.2075984","DOIUrl":"10.1080/10717544.2022.2075984","url":null,"abstract":"<p><p>At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative <i>in situ</i> recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1595-1607"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44410326","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}