RESUMEN

Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.

RESUMEN

Dried toad skin (TS) and toad venom (TV) are the dried skin of the Bufo bufo gargarizans Cantor and the Bufo melanostictus Schneider, which remove the internal organs and the white secretions of the skin and retroauricular glands. Since 2005, cinobufacini preparations have been approved by the State Food and Drug Administration for use as adjuvant therapies in the treatment of various advanced cancers. Meanwhile, bufalenolides has been identified as the main component of TS/TV, exhibiting antitumor activity, inducing apoptosis of cancer cells and inhibiting cancer cell proliferation or metastasis through a variety of signaling pathways. However, clinical agents frequently face limitations such as inherent toxicity at high concentrations and insufficient tumor targeting. Additionally, the development and utilization of these active ingredients are hindered by poor water solubility, low bioavailability, and rapid clearance from the bloodstream. To address these challenges, the design of a targeted drug delivery system (TDDS) aims to enhance drug bioavailability, improve targeting within the body, increase drug efficacy, and reduce adverse reactions. This article reviews the TDDS for TS/TV, and their active components, including passive, active, and stimuli-responsive TDDS, to provide a reference for advancing their clinical development and use.

Asunto(s)

Venenos de Anfibios , Bufanólidos , Piel , Animales , Venenos de Anfibios/química , Venenos de Anfibios/farmacología , Venenos de Anfibios/farmacocinética , Humanos , Piel/efectos de los fármacos , Piel/química , Bufanólidos/química , Bufanólidos/farmacología , Bufanólidos/farmacocinética , Bufanólidos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Bufo bufo , Bufonidae , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Neoplasias/tratamiento farmacológico , Disponibilidad Biológica

RESUMEN

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l-arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS.

Asunto(s)

Lesión Pulmonar Aguda , Arginina , Quitosano , Curcumina , Nanopartículas , Curcumina/administración & dosificación , Curcumina/farmacología , Curcumina/química , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Arginina/química , Nanopartículas/química , Ratones , Ratas , Masculino , Quitosano/química , Administración por Inhalación , Células RAW 264.7 , Ratas Sprague-Dawley , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/química

RESUMEN

Gemcitabine (GEM) is a nucleoside analogue approved as a first line of therapy for pancreatic ductal adenocarcinoma (PDAC). However, rapid metabolism by plasma cytidine deaminase leading to the short half-life, intricate intracellular metabolism, ineffective cell uptake, and swift development of chemoresistance downgrades the clinical efficacy of GEM. ONC201 is a small molecule that inhibits the Akt and ERK pathways and upregulates the TNF-related apoptosis-inducing ligand (TRAIL), which leads to the reversal of both intrinsic and acquired GEM resistance in PDAC treatment. Moreover, the pancreatic cancer cells that were able to bypass apoptosis after treatment of ONC201 get arrested in the G1-phase, which makes them highly sensitive to GEM. To enhance the in vivo stability of GEM, we first synthesized a disulfide bond containing stearate conjugated GEM (lipid-GEM), which makes it sensitive to the redox tumor microenvironment (TME) comprising high glutathione levels. In addition, with the help of colipids 1,2-dioleoyl-glycero-3-phosphocholine (DOPC), cholesterol, and 1,2-distearoyl-glycero-3-phosphoethanolamine-poly(ethylene glycol)-2000 (DSPE-PEG 2000), we were able to synthesize the lipid-GEM conjugate and ONC201 releasing liposomes. A cumulative drug release study confirmed that both ONC201 and GEM showed sustained release from the formulation. Since MUC1 is highly expressed in 70-90% PDAC, we conjugated a MUC1 binding peptide in the liposomes which showed higher cytotoxicity, apoptosis, and cellular internalization by MIA PaCa-2 cells. A biodistribution study further confirmed that the systemic delivery of the liposomes through the tail vein resulted in a higher accumulation of drugs in orthotopic PDAC tumors in NSG mice. The IHC of the excised tumor grafts further confirmed the higher apoptosis and lower metastasis and cell proliferation. Thus, our MUC1 targeting binary drug-releasing liposomal formulation showed higher drug payload, enhanced plasma stability, and accumulation of drugs in the pancreatic orthotopic tumor and thus is a promising therapeutic alternative for the treatment of PDAC.

Asunto(s)

Desoxicitidina , Gemcitabina , Neoplasias Pancreáticas , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/farmacología , Animales , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Humanos , Línea Celular Tumoral , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/farmacocinética , Apoptosis/efectos de los fármacos , Liposomas/química , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Antineoplásicos/química , Antineoplásicos/farmacología

RESUMEN

Rheumatoid Arthritis (RA) is a chronic, inflammatory, auto-immune disease that is majorly associated with the degradation of the synovial linings of the joints. It is a progressive disease that reduces the life span in affected individuals. Nanoparticles involving hyaluronic acid (HA) have gained the limelight for designing target-specific and more effective drug delivery options for RA. HA is found abundantly in the synovial fluid and acts as a natural ligand for the CD44 receptors. The targeted delivery approach using CD44 as the target can help in minimizing off-target drug distribution. These HA-based surface-decorated nanocarriers, hydrogels, and MNs are cutting-edge strategies that promise tailored delivery, fewer side effects, and more patient adherence to address the common issues associated with RA therapy. Considering the above facts, this review attempts to discuss the role of HA in making more effective formulations for therapeutic delivery in treating RA. Additionally, it provides a comprehensive overview of the potential advancements, mainly in treating RA by HA-based topical, transdermal, and parenteral drug delivery systems, with relevant case studies. The existing difficulties and potential paths for future research on HA-based non-conventional formulations for the management of RA are also discussed.

Asunto(s)

Artritis Reumatoide , Sistemas de Liberación de Medicamentos , Ácido Hialurónico , Ácido Hialurónico/química , Artritis Reumatoide/tratamiento farmacológico , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Portadores de Fármacos/química , Nanopartículas/química , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Antirreumáticos/farmacocinética , Antirreumáticos/química , Receptores de Hialuranos/metabolismo

RESUMEN

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.

RESUMEN

Diseases caused by pathogens severely hampered the development of aquaculture, especially largemouth bass virus (LMBV) has caused massive mortality and severe economic losses to the culture of largemouth bass (Micropterus salmoides). Considering the environmental hazards and human health, effective and environmentally friendly therapy strategy against LMBV is of vital importance and in pressing need. In the present study, a novel nanobody (NbE4) specific for LMBV was selected from a phage display nanobody library. Immunofluorescence and indirect ELISA showed that NbE4 could recognize LMBV virions and had strong binding capacity, but RT-qPCR evidenced that NBE4 did not render the virus uninfectious. Besides, antiviral drug ribavirin was used to construct a targeted drug system delivered by bacterial nanocellulose (BNC). RT-qPCR revealed that NbE4 could significantly enhance the antiviral activity of ribavirin in vitro and in vivo. The targeted drug delivery system (BNC-Ribavirin-NbE4, BRN) reduced the inflammatory response caused by LMBV infection and improved survival rate (BRN-L, 33.3 %; BRN-M, 46.7 %; BRN-H, 56.7 %)compared with control group (13.3 %), ribavirin group (RBV, 26.7 %) and BNC-ribavirin (BNC-R, 40.0 %), respectively. This research provided an effective antiviral strategy that improved the drug therapeutic effect and thus reduced the dosage.

Asunto(s)

Antivirales , Lubina , Celulosa , Enfermedades de los Peces , Anticuerpos de Dominio Único , Animales , Lubina/virología , Lubina/inmunología , Anticuerpos de Dominio Único/farmacología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Celulosa/química , Celulosa/farmacología , Antivirales/farmacología , Antivirales/química , Enfermedades de los Peces/virología , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/inmunología , Ribavirina/farmacología , Ribavirina/administración & dosificación , Ranavirus/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Bacterias/efectos de los fármacos

RESUMEN

Modern medicine relies on a small number of key biologics, which can be found in nature but require further characterization and purification before they can be used. Since the herbal remedy is given through a dated and ineffective method of drug administration, its effectiveness is diminished. The novel form of medicine delivery has the potential to increase the effectiveness of herbal substances while decreasing their side effects. This is the main idea behind utilising different ways of drug delivery in herbal treatments. Several benefits arise from novel formulations of herbal compounds as compared to their conventional counterparts. These include enhanced penetrating ability into tissues, constant delivery of effective doses, and resistance to physical and chemical degradation. Controlled and targeted delivery that include herbal components allow for more traditional dosing while simultaneously increasing their efficacy. Enhancing the biodistribution and target site accumulation of systemically administered herbal medicines is the goal of nanomedicine formulations. The field of nanotheranostics has made significant advancements in the development of herbal compounds by combining diagnostic and therapeutic functions on a single nanoscale platform. It is critically important to create a theranostic nanoplatform that is derived from plants and is intrinsically "all-in-one" for single molecules. In addition to examining the mechanistic approach to nanoparticle synthesis, this review highlights the therapeutic effects of nanoscale phytochemical delivery systems. Furthermore, we have evaluated the scope for future advancements in this field, discussed several nanoparticles that have been developed recently for herbal imaging, and provided experimental evidence that supports their usage.

Asunto(s)

Sistemas de Liberación de Medicamentos , Medicina de Precisión , Distribución Tisular , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , Nanotecnología

RESUMEN

Inflammatory bowel disease (IBD), marked by chronic gastrointestinal tract inflammation, poses a significant global medical challenge. Current treatments for IBD, including corticosteroids, immunomodulators, and biologics, often require frequent systemic administration through parenteral delivery, leading to nonspecific drug distribution, suboptimal therapeutic outcomes, and adverse effects. There is a pressing need for a targeted drug delivery system to enhance drug efficacy and minimize its systemic impact. Nanotechnology emerges as a transformative solution, enabling precise oral drug delivery to inflamed intestinal tissues, reducing off-target effects, and enhancing therapeutic efficiency. The advantages include heightened bioavailability, sustained drug release, and improved cellular uptake. Additionally, the nano-based approach allows for the integration of theranostic elements, enabling simultaneous diagnosis and treatment. Recent preclinical advances in oral IBD treatments, particularly with nanoformulations such as functionalized polymeric and lipid nanoparticles, demonstrate remarkable cell-targeting ability and biosafety, promising to overcome the limitations of conventional therapies. These developments signify a paradigm shift toward personalized and effective oral IBD management. This review explores the potential of oral nanomedicine to enhance IBD treatment significantly, focusing specifically on cell-targeting oral drug delivery system for potential use in IBD management. We also examine emerging technologies such as theranostic nanoparticles and artificial intelligence, identifying avenues for the practical translation of nanomedicines into clinical applications.

Asunto(s)

Sistemas de Liberación de Medicamentos , Enfermedades Inflamatorias del Intestino , Nanomedicina , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Nanomedicina/métodos , Animales , Nanopartículas/administración & dosificación , Nanopartículas/química

RESUMEN

Cancer is defined as the unchecked expansion of aberrant cells. Radiation, chemotherapy, and surgery are currently used in combination to treat cancer. Traditional drug delivery techniques kill healthy proliferating cells when used over prolonged periods of time in cancer chemotherapy. Due to the fact that the majority of tumor cells do not infiltrate right away, this is particularly true when treating solid tumors. A targeted drug delivery system (TDDS) is a tool that distributes medication to a selected bioactive location in a controlled manner. Nanotechnology-based delivery techniques are having a substantial impact on cancer treatment, and polymers are essential for making nanoparticulate carriers for cancer therapy. The advantages of nanotherapeutic drug delivery systems (NDDS) in terms of technology include longer half-life, improved biodistribution, longer drug circulation time, regulated and sustained drug release, flexibility in drug administration method, higher drug intercellular concentration, and others. The benefits and drawbacks of cancer nanomedicines, such as polymer-drug conjugates, micelles, dendrimers, immunoconjugates, liposomes, and nanoparticles, are discussed in this work, along with the most recent findings on polymer-based anticancer drugs.

RESUMEN

Traditional tumor treatments have the drawback of harming both tumor cells and normal cells, leading to significant systemic toxic side effects. As a result, there is a pressing need for targeted drug delivery methods that can specifically target cells or tissues. Currently, researchers have made significant progress in developing targeted drug delivery systems for tumor therapy using various targeting ligands. This review aims to summarize recent advancements in targeted drug delivery systems for tumor therapy, focusing on different targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. The review also discusses the advantages, challenges, and future prospects of these targeted drug delivery systems.

RESUMEN

Colorectal cancer (CRC) continues to be one of the most prevalent and deadliest forms of cancer worldwide, despite notable advancements in its management. The prognosis for metastatic CRC remains discouraging, with a relative 5-year survival rate for stage IV CRC patients. Conventional treatments for advanced malignancies such as chemotherapy, often face limitations in effectively targeting cancer cells resulting in off-target distribution and significant side effects. In the quest for better strategies, researchers have explored numerous alternatives. Among these, nanoparticles (NPs) specifically liposomes have emerged as one of the most promising candidates in developing targeted delivery systems for cancer therapeutics. This review discusses the current approaches employing functionalised liposomes to overcome major biological barriers in therapeutics delivery for CRC treatment. We have also shared our perspectives on the technological development of liposomes for future clinical use and highlighted a few useful insights on the material choices for future research work in CRC.

Asunto(s)

Antineoplásicos , Neoplasias Colorrectales , Nanopartículas , Humanos , Liposomas/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología

RESUMEN

In recent years, nanotechnology has been the focus of study for the cure of different diseases, among which nanosponge delivery system is one of a kind. Nano sponges are tiny, highly porous, three-dimensional nanostructures with a size range of 250nm-1µm in an amorphous or crystalline structure. Nanosponges usually act as an excipient or carrier of a drug in the different delivery systems. The type of polymers and cross-linkers, along with their concentration ratio, causes variation in nanosponges's dimension and encapsulation efficiency. Nanosponges have gained prominence in recent times due to their distinct ability to encapsulate both hydrophilic and lipophilic drugs within their internal cavity, thereby improving the solubility of drugs that have low water solubility. Virus-like size helps the nanosponges to circulate within the body without getting eliminated by the immune system until they stick to the targeted part of the body, which makes it the perfect candidate for a targeted drug delivery system and controlled delivery system as well because of its slow drug release property for a more extended period. Cyclodextrin-based nanosponges are the best choice for anticancer drug delivery as their small virus-like diameter helps them in passive targeting by enhancing the enhanced permeability and retention effect, allowing the anticancer drug to stay inside the tumour cell to show more significant therapeutic action on cancer, while for active targeting to the cancerous cell, nanosponges are attached with a ligand on it for receptor binding purpose. It can be used for drug delivery in many major diseases like brain-related diseases, diabetes, cancer, fungal, hypertension, etc., in different dosage forms, like oral, topical, hydrogel, parenteral, etc.

RESUMEN

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)-induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pH-dependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES 100-PEG 4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 phosphate-buffered saline and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

RESUMEN

Recently, rare diseases have received attention due to the need for improvement in diagnosed patients' and their families' lives. Duchenne muscular dystrophy (DMD) is a rare, severe, progressive, muscle-wasting disease. Today, the therapeutic standard for treating DMD is corticosteroids, which cause serious adverse side effects. Nutraceuticals, e.g., herbal extracts or essential oils (EOs), are possible active substances to develop new drug delivery systems to improve DMD patients' lives. New drug delivery systems lead to new drug effects, improved safety and accuracy, and new therapies for rare diseases. Herbal extracts and EOs combined with click chemistry can lead to the development of safer treatments for DMD. In this review, we focus on the need for novel drug delivery systems using EOs as the therapy for DMD and the potential use of click chemistry for drug delivery systems. New EO complex drug delivery systems may offer a new approach for improving muscle conditions and mental health issues associated with DMD. However, further research should identify the potential of these systems in the context of DMD. In this review, we discuss possibilities for applying EOs to DMD before implementing expensive research in a theoretical way.

RESUMEN

Brain inflammation is regarded as one of the leading causes that aggravates secondary brain injury and hinders the prognosis of ischemic stroke. After ischemic stroke, high quantities of peripheral neutrophils are recruited to brain lesions and release neutrophil extracellular traps (NETs), leading to the aggravation of blood-brain barrier (BBB) damage, activation of microglia, and ultimate neuronal death. Herein, a smart multifunctional delivery system has been developed to regulate immune disorders in the ischemic brain. Briefly, Cl-amidine, an inhibitor of peptidylarginine deiminase 4 (PAD4), is encapsulated into self-assembled liposomal nanocarriers (C-Lipo/CA) that are modified by reactive oxygen species (ROS)-responsive polymers and fibrin-binding peptide to achieve targeting ischemic lesions and stimuli-responsive release of a drug. In the mouse model of cerebral artery occlusion/reperfusion (MCAO), C-Lipo/CA can suppress the NETs release process (NETosis) and further inhibit the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway in an ischemic brain. In addition, MCAO mice treated with C-Lipo/CA significantly mitigated ischemic and reperfusion injury, with a reduction in the area of cerebral infarction to 12.1%, compared with the saline group of about 46.7%. These results demonstrated that C-Lipo/CA, which integrated microglia regulation, BBB protection, and neuron survival, exerts a potential therapy strategy to maximize ameliorating the mortality of ischemic stroke.

Asunto(s)

Trampas Extracelulares , Accidente Cerebrovascular Isquémico , Animales , Ratones , Interferones , Nucleótidos Cíclicos

RESUMEN

Elemene (ELE) is a group of broad-spectrum anticancer active ingredients with low toxicity extracted from traditional Chinese medicines (TCMs), such as Curcumae Rhizoma and Curcuma Radix, which can exert antitumour activities by regulating various signal pathways and targets. However, the strong hydrophobicity, short half-life, low bioavailability and weak in vivo targeting ability of ELE restrict its use. Targeted drug delivery systems based on nanomaterials are among the most viable methods to overcome these shortcomings. In this review, we first summarize recent studies on the clinical uses of ELE as an adjunct antitumour drug. ELE-based combination strategies have great promise for enhancing efficacy, reducing adverse reactions, and improving patients' quality of life and immune function. Second, we summarize recent studies on the antitumour mechanisms of ELE and ELE-based combination strategies. The potential mechanisms include inducing pyroptosis and ferroptosis, promoting senescence, regulating METTL3-mediated m6A modification, suppressing the Warburg effect, and inducing apoptosis and cell cycle arrest. Most importantly, we comprehensively summarize studies on the combination of targeted drug delivery systems with ELE, including passively and actively targeted drug delivery systems, stimuli-responsive drug delivery systems, and codelivery systems for ELE combined with other therapies, which have great promise in improving drug bioavailability, increasing drug targeting ability, controlling drug release, enhancing drug efficacy, reducing drug adverse effects and reversing MDR. Our summary will provide a reference for the combination of TCMs such as ELE with advanced targeted drug delivery systems in the future.

Asunto(s)

Neoplasias , Sesquiterpenos , Humanos , Calidad de Vida , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Metiltransferasas

RESUMEN

The object of the current study was to develop and evaluate trastuzumab-conjugated Paclitaxel (PTX) and Elacridar (ELA)-loaded PEGylated pH-sensitive liposomes (TPPLs) for site-specific delivery of an anticancer drug. In this study, paclitaxel is used as an anticancer drug which promotes microtubules polymerization and arrest cell cycle progression at mitosis and subsequently leading to cell death. The single use of PTX causes multiple drug resistance (MDR) and results failure of the therapy. Hence, the combination of PTX and P-glycoprotein inhibitor (ELA) are used to achieve maximum therapeutic effects of PTX. Moreover, monoclonal antibody (trastuzumab) is used as ligand for the targeting the drug bearing carriers to BC. Thus, trastuzumab anchored pH-sensitive liposomes bearing PTX and ELA were developed using thin film hydration method and Box-Behnken Design (BBD) for optimizing various formulation variables. The optimized liposomes undergo characterization such as vesicle size, PDI, and zeta potential, which were observed to be 122 ± 2.14 nm, 0.224, and -15.5 mV for PEGylated pH-sensitive liposomes (PEG-Ls) and 134 ± 1.88 nm, 0.238, and -13.98 mV for TPPLs, respectively. The results of the in vitro drug release study of both formulations (PEG-Ls and TPPLs) showed enhanced percentage drug release at an acidic pH 5 as compared to drug release at a physiological pH 7.4. Further, the in vitro cytotoxicity studies were performed in the SK-BR-3 and MDA-MB-231 cell lines. The cellular uptake study of FITC-loaded TPPLs in SK-BR-3 cells showed greater uptake than FITC-loaded PEG-Ls, while in MDA-MB-231 cells there was no significant difference in cell uptake between FITC-loaded TPPLs and FITC-loaded PEG-Ls. Hence, it can be concluded that the HER-2 overexpressing cancer cell line (SK-BR-3) was showed better cytotoxicity and cell uptake of TPPLs than the cells that expressed low levels of HER2 (MDA-MB-231). The in vivo tumor regression study, TPPLs showed significantly more tumor burden reduction i.e. up ∼74% as compared to other liposomes after 28 days. Furthermore, the in vivo studies of TPPLs showed a minimal toxicity profile, minimal hemolysis, higher tumor tissue distribution, and superior antitumor efficacy as compared to other formulations. These studies confirmed that TPPLs are a safe and efficacious treatment for breast cancer.

RESUMEN

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Curcumina , Femenino , Humanos , Curcumina/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Antineoplásicos/farmacología , Solubilidad , Portadores de Fármacos/química

RESUMEN

OBJECTIVE: To investigate the therapeutic effect of targeted drug-loaded nanoparticles modified by transferrin receptor monoclonal antibody (TfR mAb) on acute leukemia and its potential anti-tumor mechanism. METHODS: Nanoparticles drug delivery system, which was composed of poly (lactic-co-glycolic acid), poly-l-lysine, polyethylene glycol, TfR mAb (TfR mAb-PLGA-PLL-PEG)-daunorubicin (DNR), was first synthesized. After drug intervention, the intracellular accumulation in leukemia HL60 cells was observed under a fluorescent microscope and concentration of DNR was determined by flow cytometry (FCM). Meanwhile, cell apoptosis rate was measured by FCM and the expression levels of apoptosis related protein Cleaved-caspase 3 was determined by Western blot. RESULTS: Under an inverted fluorescent microscope, intracellular accumulation of DNR autofluorescence in HL60 cells was observed in both TfR mAb-PLGA-PLL-PEG-DNR group and DNR group. FCM analysis showed that the intracellular concentration of DNR in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that in DNR group（P<0.05）. The apoptotic rate of HL60 cells in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that of DNR group（P<0.05）. Moreover, the expression levels of apoptosis-related protein Cleaved-caspase 3 in TfR mAb-PLGA-PLL-PEG-DNR group was significantly higher than that in DNR group（P<0.05）. CONCLUSION: TfR mAb-PLGA-PLL-PEG nanoparticle drug delivery system can target chemotherapy drugs to leukemia cells and enhance anticancer ability through apoptotic pathway.