Current drug delivery最新文献

{"title":"The Sojourn of Polymeric Micelles for Effective Brain Drug Delivery System.","authors":"Prabhjot Kaur, Ankita Rajput, Dilpreet Singh, Gurdeep Singh, Anshula Mehra, Sarabjit Kaur, Neena Bedi, Saroj Arora","doi":"10.2174/1567201820666230413082352","DOIUrl":"10.2174/1567201820666230413082352","url":null,"abstract":"<p><p>The brain is a delicate organ and targeting neurological diseases with conventional approaches is still a daunting task. This is due to the presence of necessary physiological barriers, mainly the blood-brain barrier, that blocks the entry of dangerous and poisonous substances from the bloodstream, thus helping in maintaining homeostasis. Furthermore, the presence of multidrug resistance transporters which act by prohibiting the entry of drugs across the cell membrane and by channelizing them to the outside environment is another defense mechanism. Despite the advancements in the understanding of disease pathology, only a restricted number of drugs and drug therapies can treat and target neurological diseases. To overcome this shortcoming, the therapeutic approach using amphiphilic block copolymers - using polymeric micelles has gained momentum because of its wide applications like drug targeting, delivery, and imaging. Polymeric micelles are nanocarriers that arise when amphiphilic block copolymers spontaneously assemble in aqueous solutions. The hydrophobic core-hydrophilic shell configuration of these nanoparticles makes it easier to load hydrophobic drugs into the core and as a result, the solubility of these medications is improved. Micelle-based drug delivery carriers can target the brain with reticuloendothelial system uptake and produce a long-circulating effect. PMs can also be combined with targeting ligands that increase their uptake by specific cells and thus decreasing off-target effects. In the present review, we primarily focused on polymeric micelles for brain delivery along with the method of preparation, mechanism of micelle formulation, and the ongoing formulations under clinical trials for brain delivery.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"65-79"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317670","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":"Calixarene: A Supramolecular Material for Treating Cancer.","authors":"Rui Li, Ning Liu, Rui Liu, Xin Jin, Zheng Li","doi":"10.2174/1567201820666230417084210","DOIUrl":"10.2174/1567201820666230417084210","url":null,"abstract":"<p><p>Cancer is a disease with a high mortality rate; therefore, research on new treatment strategies is essential. There has been increased interest in novel drug delivery systems (DDS) in recent years, such as calixarene, one of the most important principal molecules in supramolecular chemistry. Calixarene is a cyclic oligomer of phenolic units linked by methylene bridges that belongs to the third generation of supramolecular compounds. By modifying the phenolic hydroxyl end (lower edge) or the para-position, a wide range of calixarene derivatives can be obtained (upper edge). Drugs are combined with calixarenes to modify and have new properties, such as strong water solubility, the ability to bond with guest molecules, and excellent biocompatibility. In this review, we summarize the applications of calixarene in the construction of anticancer drug delivery systems and its application in clinical treatment and diagnosis. It provides theoretical support for the diagnosis and treatment of cancer in the future.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"184-192"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9440206","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":"Protein Nanoparticles Laden <i>In situ</i> Gel for Topical Ocular Drug Delivery.","authors":"Archana Rajan Pillai, Bijal Prajapati, Abhay Dharamsi","doi":"10.2174/1567201820666230123140249","DOIUrl":"10.2174/1567201820666230123140249","url":null,"abstract":"<p><p>Topical ocular delivery of drugs is most commonly preferred route by the patient and physician for the treatment of ocular diseases. The topical route is always followed with the disadvantages like tear turnover, nasolacrimal drainage, reduction in precorneal residence time, etc</i>. To overcome these hindrances associated with topical ocular route, a novel drug delivery system is used for targeting the drug at a specific site. In the Novel Drug delivery System, protein-based nanoparticles are an attractive class of nanoparticles designed to deliver the drug at targeted site in slow and sustained release manner. They have a size in the range of 1-100 nm. Protein nanoparticles are leading, particularly for the topical ocular delivery like reduction in intra ocular pressure, providing sustained release and targeted drug delivery at the site of its action. Various methods are used for formulation of protein nanoparticles like desolvation, emulsification, complex coacervation, electrospray techniques. The characterization parameters include particle size, surface morphology, drug loading and entrapment efficiency. Protein nanoparticles can also be loaded in to the in situ</i> gel forming polymers for increasing precorneal residence time of nanoparticles. The characterization parameters of in situ</i> gelling systems are gelling time, rheological properties, gel strength. The review mainly describes the use of various proteins in preparation of protein nanoparticles, methods for preparation of protein nanoparticles, polymers used in in situ</i> gelling system and evaluation as well as characterization parameters of protein nanoparticles, in situ</i> gelling systems & patented information related to protein nanoparticles and in situ</i> gelling system for ocular drug delivery.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"38-51"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10615644","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":"Roxithromycin and rhEGF Co-loaded Reactive Oxygen Species Responsive Nanoparticles for Accelerating Wound Healing.","authors":"Jun Ding, Dan Chen, Jun Hu, Dinglin Zhang, Yajun Gou, Yaguang Wu","doi":"10.2174/1567201820666230512103750","DOIUrl":"10.2174/1567201820666230512103750","url":null,"abstract":"<p><strong>Background: </strong>Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation.</p><p><strong>Objective: </strong>Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat <i>Staphylococcus aureus</i>-infected wounds.</p><p><strong>Methods: </strong>By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The <i>in vivo</i> efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds.</p><p><strong>Results: </strong>ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The <i>in vitro</i> antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The <i>in vivo</i> animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"753-762"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9462868","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 Evaluation of the <i>In situ</i> Gel-forming Chitosan Hydrogels for Nasal Delivery of Morphine in a Single Unit dose in Rats to Enhance the Analgesic Responses.","authors":"Hossein Kamali, Mohsen Tafaghodi, Farhad Eisvand, S Mohammad Ahmadi-Soleimani, Mina Khajouee, Hosnieh Ghazizadeh, Jafar Mosafer","doi":"10.2174/1567201820666230724161205","DOIUrl":"10.2174/1567201820666230724161205","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, an <i>in situ</i> gel-forming chitosan hydrogel was prepared with the use of glutamate salt of chitosan (Ch-Ga), β-glycerophosphate (Gp), and morphine (Mor). The paper is focused on <i>in vitro</i> physicochemical properties and <i>in-vivo</i> analgesic effects of the prepared chitosan hydrogel.</p><p><strong>Method: </strong>The thermosensitive properties of prepared chitosan hydrogel were evaluated during the different temperatures and times. The physicochemical properties of chitosan hydrogel were investigated by infrared (IR) spectroscopy and X-ray diffraction analysis (XRD). Also, its cell cytotoxicity effects were evaluated in murine NIH/3T3 normal cells. Subsequently, the distribution of chitosan hydrogel in the nasal cavity of rats and its analgesic responses were evaluated. The prepared chitosan hydrogel showed that it could be gelled at the temperature of 34 °C before leaving the nose in the shortest possible time of 30 s.</p><p><strong>Result: </strong>The analgesic responses of the intranasal (IN) injection of chitosan hydrogel (IN-chitosan hydrogel, 10 mg Mor/kg) in a single unit dose in rat relative to the placebo and intranasal or intraperitoneal (IP) injection of free morphine solution (IN-Free Mor or IP-Free Mor, 10 mg Mor/kg) via the hot plate test, reveal that the IN-chitosan hydrogel could induce fast analgesic effects of morphine with maximum possible effect (MPE) of 93% after 5 min compare to the IN-Free Mor and IP-Free Mor with MPE of 80% after 15 min and 66% after 30 min, respectively. Also, prolonged analgesic effects with MPE of 78 % after 6 h of injection were only seen in the IN-chitosan hydrogel injected group. The obtained fluorescent images of rat's brain injected with IN-chitosan hydrogel containing doxorubicine (Dox) as a fluorescent agent showed that the mucosal adhesive and absorption enhancer properties of IN-chitosan hydrogel resulting in longer presence of them in the nasal cavity of rats followed by more absorption of Dox from the blood vessels of olfactory bulbs with a 74% color intensity compared to the IN-Free Mor and IN-Free Dox with 15%.</p><p><strong>Conclusion: </strong>These data reveal that the IN-chitosan hydrogel could induce fast and prolonged analgesic effects of morphine compare to the IN/IP-Free Mor, which could be considered as an <i>in situ</i> gel-forming thermosensitive chitosan hydrogel for nasal delivery of wide ranges of therapeutic agents.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"1024-1035"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229131","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":"Dysprosium-containing Cobalt Sulfide Nanoparticles as Anticancer Drug Carriers.","authors":"Govindaraj Sri Varalakshmi, Charan Singh Pawar, Varnitha Manikantan, Archana Sumohan Pillai, Aleyamma Alexander, Bose Allben Akash, N Rajendra Prasad, Israel V M V Enoch","doi":"10.2174/1567201821666230817122011","DOIUrl":"10.2174/1567201821666230817122011","url":null,"abstract":"<p><strong>Background: </strong>Among various materials designed for anticancer drug transport, sulfide nanoparticles are uniquely intriguing owing to their spectral characteristics. Exploration of newer nanoscale copper sulfide particles with dysprosium doping is reported herein. It leads to a change in the physicochemical properties of the sulfide nanoparticles and hence the difference in drug release and cytotoxicity.</p><p><strong>Objective: </strong>We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles.</p><p><strong>Method: </strong>The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-β-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated <i> in vitro</i>. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity <i>in vitro</i> on MCF-7 cells.</p><p><strong>Results: </strong>The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC₅₀ of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 μg mL^-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC₅₀ value is 9.7 ± 0.3 μg mL^-1.</p><p><strong>Conclusion: </strong>The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, <i>i.e.</i>, magnetic and NIR-absorbing, and are promising drug delivery agents.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"1128-1141"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023664","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":"A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of Inflammatory Arthritis <i>via</i> Draining Lymph Node.","authors":"Chenglong Li, Guanting Lu, Yue Jiang, Huaiyu Su, Chen Li","doi":"10.2174/1567201821666230810115230","DOIUrl":"10.2174/1567201821666230810115230","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production.</p><p><strong>Aim: </strong>The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG₂₀₀₀ and Ca(OH)₂.</p><p><strong>Methods: </strong>A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG₂₀₀₀ and Ca(OH)₂ were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The <i>in vivo</i> fluorescence imaging system was used to study the <i>in vivo</i> LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model.</p><p><strong>Results: </strong>Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. <i>In vivo</i> investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.</p><p><strong>Conclusion: </strong>NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"1106-1113"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977307","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":"Nanomaterials as a Potential Target for Infectious Parasitic Agents.","authors":"Rawan H Alsharedeh, Meriem Rezigue, Rasha M Bashatwah, Haneen Amawi, Alaa A A Aljabali, Mohammad A Obeid, Murtaza M Tambuwala","doi":"10.2174/1567201820666230223085403","DOIUrl":"10.2174/1567201820666230223085403","url":null,"abstract":"<p><p>Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"828-851"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758438","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":"Stem Cells and Tumor-Killing Virus to Target Brain Tumor: In Pursuit to Bring a Potential Delivery Vehicle for the Central Nervous System Tumors.","authors":"Vignesh Balaji E, K Sreedhara Ranganath Pai","doi":"10.2174/1567201820666230220101052","DOIUrl":"10.2174/1567201820666230220101052","url":null,"abstract":"<p><p>To target brain cancer, various therapeutic options are present to fight against cancer cells. But the existing therapies are not showing a proper curation of cancer patients. Henceforth, activating the immune cells and targeting oncogenes/proteins might be an emerging therapeutic approach to target and destroy malignant brain tumor. Stem cells (SCs) are considered potential immunomodulators that trigger the highly suppressed immune system in the tumor microenvironment. Also, engineered SCs can repress the aberrantly expressed oncoproteins that cause tumor cell proliferation and growth. SCs have an excellent migration capability to reach the infected site and support the regeneration of damaged blood vessels and tissues. Likewise, oncolytic virotherapy (OVT) is a promising novel therapeutic molecule in which genetically modified viruses can selectively replicate and destroy cancer cells without harming healthy cells. Same as SCs, oncolytic viruses (OVs) tend to stimulate the host's innate and adaptive immune response to battle against the advanced brain tumor. In clinical studies, various OVs have shown good immunogenic responses with a high safety profile and tolerability against cancer patients with reduced morbidity and mortality rate. SCs act as an attractive cargo for OVs which helps to influence the tumor site and destroy the tumor volume. SCs protect the OVs from systemic degradation and promote therapeutic efficacy against cancer cells. SCs carried OVs might be a potential therapeutic way to bring an effective treatment option for brain tumors.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"2-15"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10775222","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":"A Novel pH-sensitive Nanocomposite Based on Graphene Oxide for Improving Doxorubicin Release.","authors":"Marziye Javaheri Kachousangi, Amir Shadboorestan, Azam Shamsian, Mohsen Amini, Fatemeh Atyabi, Mohammad Hossein Ghahremani","doi":"10.2174/1567201820666230413094206","DOIUrl":"10.2174/1567201820666230413094206","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) as a chemotherapeutic drug has been widely used for treatment of cancer but because of adverse side effects of this drug, different drug delivery systems have been tested. One of them has been immobilization of DOX on the graphene oxide (GO) sheets through non-covalent interactions (GO-DOX) with high efficiency however the release was very low and slow due to strong forces between DOX and GO.</p><p><strong>Objective: </strong>The aim of this research was to increase the release of DOX and this goal was achieved through the covalent binding of DOX to the GO-poly(ethyleneimine) 2KDa conjugate.</p><p><strong>Methods: </strong>A novel nanocarrier for delivering DOX was fabricated using GO as a basic plane for conjugating and assembling other compounds. DOX was attached to GO-poly(ethyleneimine) 2KDa conjugate via</i> a linker containing hydrazide bond. Drug loading and release was investigated at pH 7.5 and pH 5.5. Cytotoxicity was determined by MTT on MCF7 cells and compared with previous nanocarrier.</p><p><strong>Results: </strong>The fabrication of the nanocarrier and the covalent attachment of DOX to the nanocarrier were confirmed through FT-IR spectroscopy. The capacity of nanocarrier to load drug was as high as 383%. 96% of initial drug was loaded in the nanocarrier. The weight percentage of the drug in the nanocarrierdrug conjugate was 79%. Release of drug at pH 5.5 was two times more than release at pH 7.5 and this evidence supports conjugation of DOX to nanocarrier through hydrazide bond and pH-sensitivity of related bond. Because of the reliable results, ease of operation, safety and high reproducibility, MTT was chosen to evaluate the cytotoxicity of samples. Nanocarrier didn't show significant toxicity even at high concentrations. IC50 value for chemically-bound DOX to hydrazide-containing GO nanocomposite was 9.5 μg/ml whereas the IC50 value for GO-DOX was 39 μg/ml after 72 h. Loading of DOX via hydrazide bond was as low as 4% versus near 75% physical loading of drug while hydrazide bondcontaining nanocomposite was 4 to 6 fold more toxic than GO-DOX.</p><p><strong>Conclusion: </strong>Based on the obtained data, the covalent attachment of DOX to the nanocarrier through hydrazide linkers was an interesting idea that increased drug release and toxicity despite much lower percentage of covalent attachment compared to non-covalent immobilization. As could be concluded from this study, nanocarriers based on hydrazide bond could be a good candidate for drug delivery.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"140-153"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9293639","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}