RESUMEN
This study aimed to synthesize and characterize DTX-mPEG-PLA-NPs along with the development and validation of a simple, accurate, and reproducible method for the determination and quantification of DTX in mPEG-PLA-NPs. The prepared NPs were characterized using AFM, DLS, zetasizer, and drug release kinetic profiling. The RP-HPLC assay was developed for DTX detection. The cytotoxicity and anti-clonogenic effects were estimated using MTT and clonogenic assays, respectively, using both MCF-7 and MDA-MB-231 cell lines in a 2D and 3D culture system. The developed method showed a linear response, high precision, accuracy, RSD values of ≤2%, and a tailing factor ≤2, per ICH guidelines. The DTX-mPEG-PLA-NPs exhibited an average particle size of 264.3 nm with an encapsulation efficiency of 62.22%. The in vitro drug kinetic profile, as per the Krosmeyers-Peppas model, demonstrated Fickian diffusion, with initial biphasic release and a multistep sustained release over 190 h. The MTT assay revealed improved in vitro cytotoxicity against MCF-7 and MDA-MB-231 in the 2D cultures and MCF-7 3D mammosphere cultures. Significant inhibitions of the clonogenic potential of MDA-MB-231 were observed for all concentrations of DTX-mPEG-PLA-NPs. Our results highlight the feasibility of detecting DTX via the robust RP-HPLC method and using DTX-mPEG-PLA-NPs as a perceptible and biocompatible delivery vehicle with greater cytotoxic and anti-clonogenic potential, supporting improved outcomes in BC.
RESUMEN
In Pakistan, breast cancer (BC) is frequently diagnosed with advanced disease. We aimed to examine the association of breast tumor size with reasons of reporting delays, care intervals in patients with advanced disease. This cross-sectional study enrolled 392 BC patients from tertiary care hospitals. Data were collected from August 2018-March 2019. Chi-square for significance and logistic regression for association were used. Patients between 31 and 45 years of age (51%), rural residents (39%), lower-class (88.4%), no family history (17.1%), at stage-IV (36%) and patient interval >90 days (70%, p = .034) presented with large tumor size (>5 cm). Tumor size was significantly associated with area of residence (p = .043), social-class (p = .027), family history (p = .004), smoking (p = .021), nipple discharge (p = .004), recurrence (p = .024), and metastasis (p = .007). Patient-interval was associated with poor knowledge (OR;4.3,p = .0001), influence of traditional healers (OR;2.3,p = .05), religion (OR;3.9,p = .0001), finances (OR;2.4,p = .045), and competing life priorities (OR;2.9,p = .026). In-adjusted linear regression model, area of residences, education, social-class, family-history, recurrence, cancer type, and patient interval (ß;0.110,p = .030) were found to be independent predictors of tumor size. In conclusion, education, family history, area of residence, social class, recurrence, cancer stage and patient interval, co-influenced by religion, finances, life priorities, traditional healers, and poor knowledge, were independent predictors of tumor size in BC patients.
