DoE Based Optimization and Development of Spray-Dried Chitosan-Coated Alginate Microparticles Loaded with Cisplatin for the Treatment of Cervical Cancer.

BACKGROUND: The existing parenteral treatment of cervical cancer has high toxicity and poor distribution of drugs at the targeted site. PURPOSE: To formulate localized mucoadhesive cisplatin loaded microparticles based formulation to treat cervical cancer so that enhanced therapeutics benefits with low toxicity could be achieved. METHODS: Cisplatin loaded chitosan coated spray-dried microparticles were prepared by ionotropic gelation technique and optimized by Central Composite Design. The spray-dried uncoated and chitosan- coated microparticles were characterized for various parameters (Particle size, Morphology, Drug entrapment efficiency). In vitro drug release study was carried out in simulated vaginal fluids by dialysis membrane method. Ex vivo studies were carried out to evaluate the cytotoxic potential of the developed formulation by the MTT assay. A drug permeability study was performed by Franz diffusion cell using the vaginal tissue of Swiss Albino Mice. RESULTS: All in vitro characterization parameters were found to be optimum. The in vitro release studies indicated a controlled release following the Higuchi model. The chitosan-coated microparticles were found to be more cytotoxic than uncoated microparticles and plain cisplatin solution. The chitosan-coated microparticles were found to be more permeable than uncoated microparticles. Finally, in vivo tumor regression and histopathological studies confirmed the significant decrease in tumor volume at different time intervals. CONCLUSION: Thus, it can be concluded that mucoadhesive spray-dried microparticles could provide a favorable approach for localized delivery of the anticancer drug via vaginal route against cervical cancer with its enhanced effectiveness.

Saliva collection methods for DNA biomarker analysis in oral cancer patients.

Patients with head and neck cancers are predisposed to local recurrence and second primaries because of the phenomenon of field cancerisation, and clinical detection of recurrence remains challenging. DNA biomarkers in saliva may prove to be an adjunct to current diagnostic methods, but irradiation of the primary site often leads to xerostomia. We assessed 3 methods of collecting saliva for their ability to generate DNA of sufficient quantity and quality to use in biomarker assays. Paired saliva samples were collected from 2 groups of patients with oral squamous cell carcinoma (SCC). In the first group saliva was collected in Oragene(®) vials and as saline mouthwash from non-irradiated patients (n=21) (4 had had radiotherapy before collection); in the second group it was collected using Oragene(®) sponge kits and as mouthwash from irradiated patients (n=24). Quantitative polymerase chain reaction (qPCR) showed that Oragene(®) vials contained DNA in significantly greater amounts (median 122 µg, range 4-379) than mouthwash (median 17 µg, range 2-194) (p=0.0001) in the non-irradiated patients, while Oragene(®) sponge kits (median 4 µg, range 0.1-61) and mouthwash (median 5.5 µg, range 0.1-75) generated comparable concentrations of DNA from the irradiated group. All 90 samples contained DNA of sufficient quantity and quality for p16 promoter quantitative methylation-specific PCR (qMSP). While Oragene(®) vials contained the most DNA, all 3 methods yielded enough to detect DNA biomarkers using qMSP. The method of collection should depend on the compliance of the patient and oral competency.