Development and characterization of folate anchored Saquinavir entrapped PLGA nanoparticles for anti-tumor activity.
OBJECTIVE
Saquinavir (SQV) is a US-FDA approved HIV protease inhibitor (HPI) for HIV cure. The purpose of the present investigation was to develop and characterize the anticancer potential of the SQV-loaded folic acid (FA) conjugated PEGylated and non-PEGylated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) (SQV-Fol-PEG-PLGA and SQV-Fol-PLGA) employing PC-3 (human prostate) and MCF-7 (human breast) cancer cell lines.


METHODS
Developed NPs were characterized by IR, NMR, DSC, XRD, size, charge and further tested for drug loading and cellular uptake properties.


RESULTS
The entrapment efficiency was found to be 56 ± 0.60 and 58 ± 0.80 w/v for SQV-Fol-PEG-PLGA and SQV-PLGA NPs, respectively. The obtained results of SQV-Fol-PEG-PLGA showed enhanced cytotoxicity and cellular uptake and were most preferentially taken up by the cancerous cells via folate receptor-mediated endocytosis (RME) mechanism. At 260 µM concentration, SQV-PLGA NPs and SQV-Fol-PEG-PLGA NPs showed 20%, 20% and 23% cell growth inhibition in PC-3 cells, respectively whereas in MCF-7 cells it was 12%, 15% and 14% cell growth inhibition, respectively.


CONCLUSIONS
Developed targeted SQV-Fol-PEG-PLGA NPs were superior anticancer potential as compared to non-targeted SQV-PLGA NPs. Thus, these targeted NPs provide another option for anticancer drug delivery scientists.
a Department of Zoology , Dr. H. S. Gour University , Sagar , India .
Ruchi
R
Singh
b Department of Pharmaceutical Sciences , Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit , MI , USA .
Prashant
P
Kesharwani
c Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. H. S. Gour Central University , Sagar , India .|d Pharmaceutical Nanotechnology Research Laboratory , ISF College of Pharmacy , Moga , Punjab , India , and.
Neelesh Kumar
NK
Mehra
e Indian Institute of Integrative Medicine (IIIM) , Jammu , India.
Shashank
S
Singh
a Department of Zoology , Dr. H. S. Gour University , Sagar , India .
Smita
S
Banerjee
c Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. H. S. Gour Central University , Sagar , India .
N K
NK
Jain
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D019258:Saquinavir / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D005492:Folic Acid; D019258:Saquinavir
Anti-tumor activity; Saquinavir; drug targeting; folic acid; nanoparticles