A combinatorial approach of inclusion complexation and dendrimer synthesization for effective targeting EGFR-TK

• Published in: Materials Science & Engineering C Vol. 76; pp. 959 - 965
• Main Authors: Shende, Pravin, Patil, Sampada, Gaud, R.S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2017; Elsevier BV
• Subjects: beta-Cyclodextrins; Cancer; Chemical synthesis; Combinatorial analysis; Complexation; Conjugation; Controlled release; Dendrimers; Dendrimers - chemistry; Drug therapy; Efficiency; Encapsulation; Epidermal growth factor receptors; Gefitinib; Green chemistry; Green development; Humans; Inclusion complexation; Lung cancer; Lung Neoplasms; Materials science; Non-small cell lung carcinoma; PEGylated PAMAM dendrimers; Solubility; Toxicity; β-Cyclodextrin; Inclusion complexation; PEGylated PAMAM dendrimers; Gefitinib; β-cyclodextrin; G4
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2017.03.184

The aim of the present study was to use a combinatorial approach of inclusion complexation and dendrimer synthesization of gefitinib using solvent-free technique for targeting EGFR-TK to treat Non-Small-Cell Lung Cancer (NSCLC). The inclusion complex of gefitinib with β-cyclodextrin was prepared by trituration method. This complex encapsulated G4 PAMAM dendrimers were synthesized by Michael addition and amidation reactions using green chemistry and then PEGylated by conjugation reaction. FTIR and DSC confirmed the formation of inclusion complex of gefitinib and β-cyclodextrin and PEGylation of G4 PAMAM dendrimers. Gefitinib showed higher solubility, encapsulation efficiency and controlled release profile from PEGylated dendrimers compared to inclusion complex. The PEGylated dendrimers of inclusion complex of gefitinib were found to reduce hemolytic toxicity and lesser GI 50 value on Human lung cancer cell line A-549 by effective targeting EGFR-TK. A combinatorial approach of inclusion complexation and dendrimer synthesization is one of the alternative advanced approaches to treat NSCLC. [Display omitted] •Solvent-free technique was used for dendrimer synthesis.•Solubility of gefitinib was improved due to inclusion complexation and dendrimeric network.•Effective targeting to EGFR-TK and inhibition to spread of cancer cells in the body was achieved.•PEGylated dendrimer is one of the alternative to advance approaches to treat NSCLC.