Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.
Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer.
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221 005, India. Electronic address: sanjeevbiochem11@gmail.com.
Sanjeev K
SK
Pandey
School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
Dinesh K
DK
Patel
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221 005, India.
Akhilendra K
AK
Maurya
Cell Death Research Laboratory, Division of Endocrinology, Central Drug Research Institute, Lucknow 226031, India.
Ravi
R
Thakur
Cell Death Research Laboratory, Division of Endocrinology, Central Drug Research Institute, Lucknow 226031, India.
Durga P
DP
Mishra
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221 005, India.
Manjula
M
Vinayak
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221 005, India.
Chandana
C
Haldar
School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India. Electronic address: pmaiti.mst@itbhu.ac.in.
Pralay
P
Maiti
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000473:pathology; D001682:Biological Availability; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053837:DNA Cleavage / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D065546:Drug Liberation; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013629:Tamoxifen / Q000494:pharmacology
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D013629:Tamoxifen; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol
Controlled release; Emulsified nanoprecipitation; Nanoparticles; PLGA; Tamoxifen