Polymer-drug conjugates are nano-medicine products under development for cancer diagnosis and treatment.[1] There are more than 10 anticancer conjugates in clinical development. Polymer-drug conjugates are drug molecules held in polymer molecules, which act as the delivery system for the drug. Polymer drugs have passed multidrug resistance (MDR) testing and hence may become a viable treatment for endocrine-related cancers. A cocktail of pendant drugs could be delivered by water-soluble polymer platforms. The physical and chemical properties of the polymers used in polymer-drug conjugates are specially synthesized to flow through the kidneys and liver without being filtered out, allowing the drugs to be used more effectively. Traditional polymers used in polymer-drug conjugates can be degraded through enzymatic activity and acidity. Polymers are now being synthesized to be sensitive to specific enzymes that are apparent in diseased tissue. The drugs remain attached to the polymer and are not activated until the enzymes associated with the diseased tissue are present. This process significantly minimizes damage to healthy tissue.[2][3]
Most typical deliver of drugs is through the mouth, skin, transmucosal and inhalation. Drug polymer conjugate follow these to some degree, but they are usually administered via injection. Many enzymes in the body decompose the drug if the drug is taken by other means.[4]
Currently Being Testededit
The polymer-drug N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer-doxorubicin (PK1; FCE28068) shows up to a 5 times reduction in anthracycline type toxicity compared to current treatments. Doses up to 1680 mg/m2 observed no cardiotoxicity. Antitumor behavior was observed at 80–320 mg/m2 of doxorubicin.
Polymers are used for the delivery of drugs and proteins. Some types of polymers being tested now are poly(ethylene glycol) (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), and poly(lactide-co-glycolide) (PLGA) copolymers have been successful in medical research. Recently there has been a growing interest in polymer conjugation with biologically active components. Such conjugates usually accumulate in tumors and can reduce toxicity in the body. Depending on the desired location, polymer conjugates can be synthesized to either have degradable or non-degradable chemical bonds with their associated drug. To obtain many of many of these bonds the use of peptides or amino acids. There is a strong desire to synthesize polymeric conjugates with bioactive components and other drugs. The tendency of polymer drug conjugate to react with the proper type cell(s) needs to still be worked on, despite many current advances.[5]
Novel Polymer-Based Combinationsedit
By now only traditional chemotherapeutic agents like doxorubicin, paclitaxel, camptothecins and platinates[check spelling] have been clinically tested in drug conjugates. Due to successful clinical proof-of-concept, second-generation conjugates are now being developed. Experimental chemotherapy and novel polymer-based combinations are currently under investigation. Instead of passive targeting developed so far, new approaches will provide receptor-mediated delivery. This will enable selective delivery of anticancer conjugates.
A natural polymer dextrin and pendant chain polyacetals, have shown ability of pH-dependent degradation after incorporation into cell compartments. Also diethylstilboestrol (DES) conjugates can undergo pH-dependent degradation. Polymer-Directed Enzyme Prodrug Therapy (PDEPT) is an example of two-step anticancer treatment.[6]
Referencesedit
^Feng, Q; Tong, R (2016). "Anticancer nanoparticulate polymer‐drug conjugate". Bioengineering & Translational Medicine. American Institute of Chemical Engineers. 1 (3): 277–296. doi:10.1002/btm2.10033. PMC5689533. PMID 29313017.
^Bertrand, Nicolas; Leroux, Jean-Christope (2012). "The Journey of a Drug-carrier in the Body: An Anatomo-physiological Perspective". Institute of Pharmaceutical Sciences. 161 (2): 152–63. doi:10.1016/j.jconrel.2011.09.098. PMID 22001607.
^Chau, Ying (2005). Targeted drug delivery by novel polymer-drug conjugates containing linkers cleavable by disease-associated enzymes (Thesis). hdl:1721.1/32332.
^Duncan, R; Vincent, M J (2005). "Polymer-drug Conjugates: Towards a Novel Approach for the Treatment of Endrocrine-related Cancer". Endocrine-Related Cancer. Bioscientifica. 12: 189–199. doi:10.1677/erc.1.01045. PMID 16113096.
^Khandare, Jayant; Minko, Tamara (April 2006). "Polymer–drug conjugates: Progress in polymeric prodrugs". Progress in Polymer Science. 31 (4): 359–397. doi:10.1016/j.progpolymsci.2005.09.004.
^Vicent, Maria J. (June 2007). "Polymer-drug conjugates as modulators of cellular apoptosis". The AAPS Journal. 9 (2): E200–E207. doi:10.1208/aapsj0902022. PMC2751409. PMID 17907762.
March 16, 2024
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Polymer drug conjugates are nano medicine products under development for cancer diagnosis and treatment 1 There are more than 10 anticancer conjugates in clinical development Polymer drug conjugates are drug molecules held in polymer molecules which act as the delivery system for the drug Polymer drugs have passed multidrug resistance MDR testing and hence may become a viable treatment for endocrine related cancers A cocktail of pendant drugs could be delivered by water soluble polymer platforms The physical and chemical properties of the polymers used in polymer drug conjugates are specially synthesized to flow through the kidneys and liver without being filtered out allowing the drugs to be used more effectively Traditional polymers used in polymer drug conjugates can be degraded through enzymatic activity and acidity Polymers are now being synthesized to be sensitive to specific enzymes that are apparent in diseased tissue The drugs remain attached to the polymer and are not activated until the enzymes associated with the diseased tissue are present This process significantly minimizes damage to healthy tissue 2 3 Contents 1 Method of delivery 2 Currently Being Tested 3 Novel Polymer Based Combinations 4 ReferencesMethod of delivery editMost typical deliver of drugs is through the mouth skin transmucosal and inhalation Drug polymer conjugate follow these to some degree but they are usually administered via injection Many enzymes in the body decompose the drug if the drug is taken by other means 4 Currently Being Tested editThe polymer drug N 2 Hydroxypropyl methacrylamide HPMA copolymer doxorubicin PK1 FCE28068 shows up to a 5 times reduction in anthracycline type toxicity compared to current treatments Doses up to 1680 mg m2 observed no cardiotoxicity Antitumor behavior was observed at 80 320 mg m2 of doxorubicin Polymers are used for the delivery of drugs and proteins Some types of polymers being tested now are poly ethylene glycol PEG N 2 hydroxypropyl methacrylamide HPMA and poly lactide co glycolide PLGA copolymers have been successful in medical research Recently there has been a growing interest in polymer conjugation with biologically active components Such conjugates usually accumulate in tumors and can reduce toxicity in the body Depending on the desired location polymer conjugates can be synthesized to either have degradable or non degradable chemical bonds with their associated drug To obtain many of many of these bonds the use of peptides or amino acids There is a strong desire to synthesize polymeric conjugates with bioactive components and other drugs The tendency of polymer drug conjugate to react with the proper type cell s needs to still be worked on despite many current advances 5 Novel Polymer Based Combinations editBy now only traditional chemotherapeutic agents like doxorubicin paclitaxel camptothecins and platinates check spelling have been clinically tested in drug conjugates Due to successful clinical proof of concept second generation conjugates are now being developed Experimental chemotherapy and novel polymer based combinations are currently under investigation Instead of passive targeting developed so far new approaches will provide receptor mediated delivery This will enable selective delivery of anticancer conjugates A natural polymer dextrin and pendant chain polyacetals have shown ability of pH dependent degradation after incorporation into cell compartments Also diethylstilboestrol DES conjugates can undergo pH dependent degradation Polymer Directed Enzyme Prodrug Therapy PDEPT is an example of two step anticancer treatment 6 References edit Feng Q Tong R 2016 Anticancer nanoparticulate polymer drug conjugate Bioengineering amp Translational Medicine American Institute of Chemical Engineers 1 3 277 296 doi 10 1002 btm2 10033 PMC 5689533 PMID 29313017 Bertrand Nicolas Leroux Jean Christope 2012 The Journey of a Drug carrier in the Body An Anatomo physiological Perspective Institute of Pharmaceutical Sciences 161 2 152 63 doi 10 1016 j jconrel 2011 09 098 PMID 22001607 Chau Ying 2005 Targeted drug delivery by novel polymer drug conjugates containing linkers cleavable by disease associated enzymes Thesis hdl 1721 1 32332 Duncan R Vincent M J 2005 Polymer drug Conjugates Towards a Novel Approach for the Treatment of Endrocrine related Cancer Endocrine Related Cancer Bioscientifica 12 189 199 doi 10 1677 erc 1 01045 PMID 16113096 Khandare Jayant Minko Tamara April 2006 Polymer drug conjugates Progress in polymeric prodrugs Progress in Polymer Science 31 4 359 397 doi 10 1016 j progpolymsci 2005 09 004 Vicent Maria J June 2007 Polymer drug conjugates as modulators of cellular apoptosis The AAPS Journal 9 2 E200 E207 doi 10 1208 aapsj0902022 PMC 2751409 PMID 17907762 Retrieved from https en wikipedia org w index php title Polymer drug conjugates amp oldid 1124691818, wikipedia, wiki, book, books, library,
