{"doi":"10.3390/pharmaceutics17091174","title":"Modeling and Design of Chitosan–PCL Bi-Layered Microspheres for Intravitreal Controlled Release","abstract":"Background/Objectives: Chronic retinal diseases usually require repetitive local dosing. Depending on factors such as dosing frequency, mode of administration, and associated costs, this can result in poor patient compliance. A better alternative involves using controlled-release drug delivery systems to reduce the frequency of intravitreal dosing and extend drug release. However, reaching the market stage is a time-consuming process. Methods: In this study, we employed two computational approaches to model and estimate the parameters governing the diffusion-controlled drug release from bi-layered microspheres. The case study involved microspheres composed of a chitosan core and a polycaprolactone (PCL) shell. The model drugs were bovine serum albumin and bevacizumab (an agent that slows neovascularization due to retinal disorders). Drug release from the microspheres is described by a mathematical model that was solved numerically using the finite difference and the finite element approaches. The parameter estimation was performed by nonlinear least-squares regression. Results: We used the estimated parameters to simulate the cumulative release under various conditions and optimize the device design to guide future experimental efforts and improve the duration of release beyond a target daily therapeutic release rate from the microspheres. Conclusions: We investigated the effects of polymeric layer sizes on drug release and provided recommendations for optimal sizes. We provide straightforward computational tools for others to reuse in designing bi-layered microspheres for intravitreal drug delivery needs in the treatment of chronic ocular neovascularization.","journal":"Pharmaceutics","year":2025,"id":554110,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1335144,"name":"Samantha L. Carpenter","orcid":null,"position":1,"is_corresponding":false},{"id":902691,"name":"Katelyn E. Swindle‐Reilly","orcid":"0000-0003-1739-0263","position":2,"is_corresponding":false},{"id":550759,"name":"Ashlee N. Ford Versypt","orcid":"0000-0001-9059-5703","position":3,"is_corresponding":false},{"id":1047572,"name":"Eduardo A. Chacin Ruiz","orcid":"0009-0005-2553-5647","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"41012510","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":[]}