Development of sulforaphane-encapsulated microspheres for cancer epigenetic therapy.
Even though conventional chemotherapeutic management of cancer has reduced morbidity and mortality to a great extent, virtually all chemotherapeutic agents cause damage to healthy cells, necessitating exploration of novel anticancer agents that exert their effects through an alternate mode of action. Objectives of our research were twofold. First, we explored the promising potential of histone deacetylase inhibitor sulforaphane for epigenetic therapy for cancer as this therapeutic approach aims to reverse aberrant epigenetic modifications that affect gene expression. In vitro cell culture studies performed using B16 and S91 melanoma cells showed that sulforaphane inhibited growth and proliferation of cancer cells by downregulating deacetylation enzymes. The second part of our research investigated polymeric drug delivery systems to increase therapeutic efficacy and to minimize potential side effects of R,S-sulforaphane. Albumin microspheres encapsulating sulforaphane were developed by spray drying. Microspheres were characterized for their morphology, size and zeta potential. Cell culture studies using melanoma cells and in vivo studies in melanoma tumor-bearing C57BL/6 mice demonstrated that albumin based polymeric delivery system was efficacious and has the potential to enhance the therapeutic effect and anticancer activity of sulforaphane.
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Department of Pharmaceutical Sciences, School of Pharmacy, Lake Erie College of Osteopathic Medicine, 1858 W Grandview Blvd, Erie, PA 16509, USA. duc.p.do@gmail.com
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Rizvi
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D'Souza
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D000418:Albumins / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D044127:Epigenesis, Genetic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017879:Isothiocyanates; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D013454:Sulfoxides; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013861:Thiocyanates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
D000418:Albumins; D000970:Antineoplastic Agents; D004337:Drug Carriers; D056572:Histone Deacetylase Inhibitors; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane