title: Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles.
abstract: OBJECTIVE
  Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics.
  
  
  RESULTS
  Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs.
  
  
  CONCLUSIONS
  Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India.
authors: Nishu
authors: N
authors: Dixit
authors: Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.
authors: Kumar
authors: K
authors: Vaibhav
authors: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.
authors: Ravi Shankar
authors: RS
authors: Pandey
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India.
authors: Upendra Kumar
authors: UK
authors: Jain
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors: Om Prakash
authors: OP
authors: Katare
authors: Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.
authors: Anju
authors: A
authors: Katyal
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India. Electronic address: jitenderpharmacy@gmail.com.
authors: Jitender
authors: J
authors: Madan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014961:X-Ray Diffraction
chemical_list: D011208:Powders; D005780:Gelatin; D005492:Folic Acid; D002945:Cisplatin
keywords: Apoptosis; Cellular uptake; Cervical cancer; Cisplatin; Cytotoxicity; Folate; Gelatin nanoparticles