{"doi":"10.21203/rs.3.rs-1777458/v1","title":"Application of modified gemcitabine-loaded solid lipid nanoparticle in the treatment of pancreatic cancer patient-derived xenograft model","abstract":"Abstract Purpose : Gemcitabine (Gem) remains a preferred first-line anticancer drug used for the treatment of pancreatic cancer (PCa). However, rapid metabolism and systemic instability (short half-life) have limited its therapeutic efficacy. The purpose of this study was to modify Gem to a more stable form, 4-(N)-stearoyl-gemcitabine (4NSG), and to evaluate its efficacy in patient-derived xenograft (PDX) mouse models harboring African American (AA) and Caucasian (White) patients' tumors. Methods : 4NSG was developed and characterized using high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and elemental analysis. 4NSG-loaded solid lipid nanoparticles (4NSG-SLN) were developed using the cold homogenization technique and characterized. Cytotoxicity, cell migration, and clonogenic studies were performed to determine the effectiveness of 4NSG-SLN against AA primary PCa cells (PPCL-192, PPCL-135) and White PCa primary cells (PPCL-46, PPCL-68). Pharmacokinetics (PK), and tumor efficacy studies were conducted using PDX mouse models bearing tumors from AA and white PCa patients. Results : The effective particle size of 4NSG-SLN was 82 nm and (IC 50 ) values of 4NSG-SLN treated AA cells (PPCL-192, 9 ± 1.1 µM and PPCL-135, 11 ± 1.3 µM) and White cells (PPCL-46, 12 ± 2.1 and PPCL-68, 22 ± 2.6) were found to be significantly lower compared to Gem treated AA cells (PPCL-192, 57 ± 1.5 µM and PPCL-135, 56 ± 1.5 µM) and White cells (PPCL-46, 56 ± 1.8 µM and PPCL-68, 57 ± 2.4 µM). The area under the curve (AUC), half-life, and clearance pharmacokinetic parameters for 4NSG-SLN were 3-4-fold higher compared to that of GemHCl. 4NSG-SLN treated PDX mice exhibited a two-fold decrease in tumor growth inhibition in PDX mice bearing AA and Whites patients' tumors compared to Gem treated PDX mice bearing AA and Whites tumors. Conclusion : 4NSG-SLN significantly improved the pharmacokinetics of Gem, enhanced systemic stability of Gem, and increased its antitumor efficacy in PCa PDX mice bearing AA and White tumors.","journal":"Research Square","year":2022,"id":301712,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":399270,"name":"Nkafu Bechem Ndemazie","orcid":"0000-0001-5825-2022","position":1,"is_corresponding":false},{"id":463841,"name":"Taylor Smith","orcid":"0000-0002-6763-7204","position":2,"is_corresponding":false},{"id":973160,"name":"Esther Frimpong","orcid":"0000-0001-6908-823X","position":3,"is_corresponding":false},{"id":973159,"name":"Raviteja Bulusu","orcid":"0000-0003-4613-4621","position":4,"is_corresponding":false},{"id":993752,"name":"Rosemary A. Poku","orcid":null,"position":5,"is_corresponding":false},{"id":399271,"name":"Xue Y. Zhu","orcid":"0009-0001-8425-4379","position":6,"is_corresponding":false},{"id":285049,"name":"Bo Han","orcid":"0000-0003-1458-4265","position":7,"is_corresponding":false},{"id":267423,"name":"José G. Treviño","orcid":"0000-0002-0265-8151","position":8,"is_corresponding":false},{"id":285051,"name":"Edward Agyare","orcid":"0000-0002-6905-5136","position":9,"is_corresponding":false},{"id":400793,"name":"Andriana Inkoom","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}