Lipid-Based Nanocarriers for Targeted Delivery to Pancreatic β-Cells in Obese Diabetic Models

Nantulya Morris Francis

Department of Clinical pharm and pharmaceutics Kampala International University Uganda

Email:Francis.nantulya@studwc.kiu.ac.ug

ABSTRACT

Obesity-linked type 2 diabetes is driven by chronic insulin resistance coupled to progressive dysfunction and loss of pancreatic β-cells. Standard glucose-lowering therapies improve glycemia but either protect β-cells only indirectly or require high systemic exposure, which invites adverse effects. Lipid-based nanocarriers offer a modular approach to concentrate therapeutics within β-cells while shielding labile molecules, extending residence time, and minimizing off-target exposure. By tuning lipid composition, size, surface charge, and corona, these systems can traverse gastrointestinal and vascular barriers, engage islet microvasculature, and exploit receptor-mediated endocytosis on β-cells. Contemporary designs include liposomes, solid lipid nanoparticles, nanostructured lipid carriers, ionizable lipid nanoparticles, and lipid–polymer hybrids, each adaptable to diverse payloads such as small molecules, peptides and proteins, nucleic acids, and genome editors. Targeting tactics range from GLP-1 receptor and sulfonylurea receptor–binding peptides to zinc and manganese-coordination motifs that sense the β-cell secretory niche, as well as islet endothelium–addressing ligands that facilitate transendothelial passage. In obese diabetic models, β-cell–directed lipid nanocarriers improve glucose tolerance, preserve glucose-stimulated insulin secretion, reduce endoplasmic reticulum and oxidative stress, and limit dedifferentiation, often at doses below the thresholds needed for free drugs. Translation now depends on robust potency assays that reflect β-cell–specific mechanisms, biodistribution profiling in metabolically diseased animals, cGMP manufacturing with tight control of critical quality attributes, and safety evaluations that consider complement activation and repeated-dosing kinetics in obesity. This review synthesizes the biological rationale, engineering principles, targeting strategies, therapeutic payloads, preclinical outcomes, and translational considerations for lipid-based β-cell–targeted delivery in obesity-associated diabetes.

CITE AS: Nantulya Morris Francis (2026). Lipid-Based Nanocarriers for Targeted Delivery to Pancreatic β-Cells in Obese Diabetic Models. RESEARCH INVENTION JOURNAL OF RESEARCH IN MEDICAL SCIENCES 5(1):9-17. https://doi.org/10.59298/RIJRMS/2026/51917