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1.
Int J Pharm ; 525(2): 407-417, 2017 Jun 20.
Article in English | MEDLINE | ID: mdl-28373100

ABSTRACT

Co-delivery of chemotherapeutic agents improve anti-tumor efficacy and reduce cancer resistance. Here, we report development of layer-by-layer assembled gold nanoparticles (LbL-AuNP) containing anti-STAT3 siRNA and imatinib mesylate (IM) to treat melanoma. The combination treatment with STAT3 siRNA and IM in B16F10 melanoma cells showed greater suppression of STAT3 protein, decreased cell viability and increased apoptotic events compared with LbL-AuNP containing either STAT3 siRNA or IM. In vivo efficacy studies in melanoma tumor bearing mice showed that non-invasive topical iontophoretic administration (0.5mA/cm2) of LbL-AuNP was comparable with intratumoral administration. Co-delivery of STAT3 siRNA and IM using LbL-AuNP showed significant (p<0.05) reduction in percentage tumor volume, tumor weight and suppressed STAT3 protein expression compared with either STAT3 siRNA or IM loaded LbL-AuNP. Taken together, LbL-AuNP can be developed as nanocarrier system for co-delivery of siRNA and small molecule drugs for topical iontophoretic delivery.


Subject(s)
Imatinib Mesylate/administration & dosage , Melanoma, Experimental/genetics , Metal Nanoparticles/chemistry , RNA, Small Interfering/administration & dosage , Animals , Cell Line, Tumor , Gold , Melanoma, Experimental/therapy , Mice , STAT3 Transcription Factor/genetics
2.
ACS Omega ; 2(4): 1321-1332, 2017 Apr 30.
Article in English | MEDLINE | ID: mdl-30023631

ABSTRACT

Transcutaneous antigen administration provides an alternative to invasive syringe injections. The objective of this study was to investigate the feasibility of fabrication and antigen delivery using microneedles made from corn protein, zein. Micromolding technique was used to cast cone-shaped zein microneedles (ZMNs). The insertion of ZMNs and the delivery of the model antigen, ovalbumin (OVA), into the skin was confirmed by histological examination and confocal microscopy. In addition, a significantly (p < 0.05) lower bacterial skin penetration was observed after ZMN application compared with hypodermic syringe application. OVA coated on ZMNs was stable after storage under ambient and refrigerator conditions. Transcutaneous immunization studies showed significantly (p < 0.001) greater antibody titers (total IgG, IgG1, and IgG2a) after the application of OVA-coated ZMNs and OVA intradermal injection compared with the control group. Taken together, antigen-coated ZMNs can be developed for transcutaneous vaccine delivery.

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