Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation.
Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib-polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50value against MCF-7 cells.
a Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende , CS , Italy.
Luca
L
Scrivano
a Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende , CS , Italy.
Domenico
D
Iacopetta
a Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende , CS , Italy.
Maria Stefania
MS
Sinicropi
b Department of Sciences, University of Basilicata , Potenza , Italy , and.
Carmela
C
Saturnino
c Department of Chemistry and Biology, University of Salerno , Fisciano , SA , Italy.
Pasquale
P
Longo
a Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende , CS , Italy.
Ortensia Ilaria
OI
Parisi
a Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , Rende , CS , Italy.
Francesco
F
Puoci
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D047030:Sericins / Q000138:chemical synthesis*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D000077210:Sunitinib; D013678:Technology, Pharmaceutical / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D047030:Sericins; D000077210:Sunitinib
Sericin; bioavailability; bioconjugates; cell permeability; radical grafting; sunitinib