Ligandmediated and enzymedirected precise targeting and. The major hurdle of nanostructured therapeutic agents comes from the limited retention at the gbm site and poor selectivity. Ligandmediated active targeting for enhanced oral absorption however, oral drug delivery is faced with difficulties in the case of poorly watersoluble and poorly permeable drugs, which are commonly classified as biopharmaceutical classification. Here, we used phage display to identify a novel peptide sp94, which binds specifically to hepatocellular carcinoma cells. A drug delivery system comprising a binary conjugate i. Therefore, ongoing research aims at enhancing the tumor sitespecific action of the liposomes by attaching ligands to surface molecules of tumor cells and tumor vasculature, a process called active or ligandmediated targeting liposomes 5, 6, 75. Folate targeted drug delivery has emerged as an alternative therapy for the treatment and imaging of many cancers and inflammatory diseases. One approach suggested to overcome these limitations is the inclusion of a targeting ligand or antibody in polymerdrug conjugates 4. It is a method of delivering medication to a patient in a manner that increases the. Therapeutic nanoparticles for drug delivery in cancer. Synthesis and evaluation of a novel ligand for folate.
Ligand mediated targeting known as active targeting of nanodrug has played an important role in enhancing tumor targeting efficiency danhier et al. In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The difficulty of delivering therapeutic molecules to lesions resulting from ci hinders the effective treatment of this disease. Sugar ligand molecules, such as mannose, galactose and glucose, can bind to drugdelivery systems, making them targeted. Receptormediated drug delivery systems targeting to glioma. Sugar ligandmediated drug delivery future medicinal chemistry. Antitumoral cascadetargeting ligand for il6 receptor. An essential aspect for the successful development of targeted drug delivery system relies upon the choice of targeting ligand 20. In vivo targeting of ovtl 3 immunoliposomes to ascitic ovarian carcinoma cells ovcar3 in athymic nude mice. The parameters that should be considered while selecting targeting ligand include ligand biocompatibility, cell specificity, binding affinity, purity of the ligand, size and charge of the ligand molecule, and. Pdf ligand mediated drug targeted liposomes researchgate. Ep0349127a1 ep89305461a ep89305461a ep0349127a1 ep 0349127 a1 ep0349127 a1 ep 0349127a1 ep 89305461 a ep89305461 a ep 89305461a ep 89305461 a ep89305461 a ep 89305461a ep 0349127 a1 ep0349127 a1 ep 0349127a1 authority ep european patent office prior art keywords tumor differentiation inducer ganglioside antibody prior art date 19880701 legal status the legal.
Elevated cellular drug uptake by the targeted diseased cells can be actively obtained from the proper selection of a diseasespecific receptor, a targeting ligand, and a spacer 1, 3. Institute of biostructures and bioimaging, national research council, via mezzocannone 16, 808 naples, italy. The single targeting ligand the single targeting ligand that could mediate both transportation of drugs acro ss the bbb and. The safe and efficient delivery of chemotherapeutic agents remains critical to anticancer therapy. Peptidemediated targeting to tumor blood vessels of lung cancer for drug delivery tongyoung lee, chintarng lin, szuyao kuo, dekuan chang and hanchung wu cancer res november 15 2007 67 22 1095810965. Request pdf ligand receptor mediated drug delivery. Ligand mediated drug targeted liposomes, publisher. Due to its small molecular size and high binding affinity for cell surface folate receptors fr, folate conjugates have the ability to deliver a variety of molecular complexes to pathologic cells without causing harm to normal tissues. Targeted intracellular drug delivery by receptor medicated endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. Peptide ligands are advantageous over other classes of targeting ligands due to their accessibility of highthroughput screening, ease of. In fact, scientists in the drugdelivery field have used the terms targeting, passive targeting, active targeting and targeted drug delivery in numerous. Specifically, red blood cell rbc membrane was modified with targeting peptides through a facile insertion method involving avidinbiotin interactions. Efficient binding and internalization requires that receptors are expressed exclusively on target cancer cells 10 4 10 5 copies per cell relative to normal. Some representative targets used in ligandmediated drug delivery.
Recent advances in multivalent targeting and ligand organization on. Immunoliposomemediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo. Cerebral ischemia ci results from inadequate blood flow to the brain. Therefore, development of novel tumorspecific ligands or pharmaceutical nanocarriers is highly desirable. The binding typically results in a change of conformational isomerism conformation of the target protein. Common oligosaccharides of cellularglycoconjugates are ligands for more than one type of endogenous lectin. Strategies to prepare targeting ligands highly specific for the receptor volume. Sterken, in het openbaar te verdedigen op maandag 11 juni 2012 om 14.
Deshmukh1 1rasa life science informatics, 301, dhanashree apartments, opposite chitaranjan vatika, model colony, shivaji nagar pune mh 411016, india. Because most ltds are composed of a targeting ligand e. In proteinligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. Sugar ligandmediated drug delivery future medicinal. This provides a rationale for the development of some novel. Ligandblocking and membraneproximal domain targeting. In this study, we reported dualfunctional gold nanoparticles aunps to figure out the biological barrier and improve their accumulation in gbm. Challenges in design and characterization of ligandtargeted drug.
Novel treatment strategies derived from increased knowledge of molecular oncology are constantly being developed to cure this disease. Drug delivery to the brain via an endogenous bbb transport mechanism allows for drug penetration into the complete brain, but clearly requires reformulation of the drug so that it can be recognized by such a transport mechanism. Ligandmediated gastrointestinal targeting springerlink. A dualmediated liposomal drug delivery system targeting. Active targeting employs specific modification of a drugdrug carrier nano systems with active.
Targeted intracellular drug delivery by receptor mediated. Abstractrheumatoid arthritis ra is an immunemediated inflammatory disease that selectively attacks human joints. The best method to maximize safety and efficacy is to deliver a proven therapeutic agent with a targeting ligand that exhibits little affinity for healthy cells but high affinity for pathologic cells. Pdf receptormediated drug delivery systems targeting to. Active targeting based on the ligandtarget affinity is a common strategy to precisely deliver nanoparticle np imaging probes or drug carriers to the diseased tissue. The purpose of this study is to explore distinct features ofligand presentation and structure for design of cluster glycosides. Safety and efficacy constitute the major criteria governing regulatory approval of any new drug. Ligand mediated targeting targeting components which have been studied and exploited are pilot molecules themselves bioconugate or anchored as ligands on some delivery vehicle drug carrier system, all the carrier systems in general are colloidal in nature. Targeting strategies for multifunctional nanoparticles in. Chitosan and its derivatives as vehicles for drug delivery were summarized. An emerging paradigm in cellular drug targeting if. In addition, compared with previously reported two ligandmediated targeting strategies, i 6 p 7 could act as both a bbbcrossing and a gliomatargeting ligand to realize a. Drug delivery specifically to the intracellular site of target cells. Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the nontarget organs or tissues or cells.
Drug delivery targets and systems for targeted treatment. An emerging paradigm in cellular drug targeting receptormediated cellular events have received major attention in the field of druggene. University of groningen ligandmediated transport of drug. The common nontargeted treatment approaches lead to obvious side effect and systemtic complication for ra patients. Association of a targeting ligand such as transferrin, or an endosome disrupting peptide such as gala, with cationic liposomedna complexes lipoplexes results in a significant.
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Hepatocellular carcinoma cellspecific peptide ligand for. Targeted drug delivery systems mediated by a novel peptide. Synthesis and evaluation of a novel ligand for folatemediated targeting liposomes guangya xiang, a, b, jun wu, b yanhui lu, b zhilan liu, b, c and robert j. Probing and enhancing ligandmediated active targeting of.
This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticlemediated drug delivery in order to combat the downfalls of conventional drug. Active targeting strategies using biological ligands for. Glioma has been considered to be the most frequent primary tumor within the central nervous system cns. Direct coupling of drugs to targeting ligand, restricts the coupling capacity to. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate. Lee b, d, e, a pharmacy school, tongji medical college, huazhong university of.
Preparation and evaluation of mannose receptor mediated macrophage targeting delivery system. Epitope specificity is an important consideration when designing antitnfr agonistic antibodies for cancer treatment. The probability of regulatory approval can conceivably be further enhanced by exploiting the same. Ligandmediated tissuespecific drug delivery sciencedirect. An emerging paradigm in cellular drug targeting receptor mediated cellular events have received major attention in the field of drug gene.
The inflammatory response following ci offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and. Peptidemediated drug delivery across the bloodbrain barrier for targeting brain tumors. Glioblastoma gbm, one of the most lethal cancers, remains as a hard task to handle. Peptidemediated targeting to tumor blood vessels of lung. Nanoparticles that present targeting moieties can bind to target cells through ligandreceptor interactions that induce receptormediated endocytosis and drug release inside the cell. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via rmt. Designing novel inhibitors for tuberculosis tb by targeting inha and kasa using ligand based drug design 1,s. For example, targeted drug delivery strategies have exploited the clathrindependent receptor mediated endocytic events of glycoreceptors, including mannose6phosphate receptor and mannose receptor. Peptide ligandmediated targeted drug delivery of nanomedicines.
Peptidemediated liposomal drug delivery system targeting. However, such ligandmediated active targeting inevitably takes place with prerequisite passive targeting, driven by the enhanced permeability and retention epr effect. A dualmediated liposomal drug delivery system targeting the brain. Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. This delivery mechanism provokes a highly directed method for the delivery of deficient lysosomal enzymes as well as drug precursors. Targeting receptormediated transport for delivery of. The complexity of glioma, especially the existence of the bloodbrain barrier bbb, makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. Herein, we report on a targeted drug delivery system based upon a modified cell membrane coating technique and drug nanocrystals ncs. Targeted delivery of drugs to tumors represents a significant advance in cancer diagnosis and therapy. In this study, we utilized phage display to identify a new targeting peptide, sp90, which specifically binds to breast cancer cells, and recognizes tumor tissues from breast cancer patients. Therefore, targeted drug delivery for treatment of ra has gained much attetntion in the past few years. One promising strategy for overcoming the bbb to deliver biologics is the targeting of endogenous receptormediated transport rmt systems that employ vesicular trafficking to transport ligands across the bbb endothelium. It is obvious that polymerdrug conjugates would benefit from ligandmediated targeting using internalizing ligands, given the requirement of metabolic activation for drug release.
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