Introduction: Papaya seeds are a rich source of proteins, fat, fibers, vitamins, minerals, monounsaturated fatty
acids, polyphenols, and powerful antioxidants like flavonoids. Carica papaya is used for treating skin, fungal,
viral, digestive, and dental disorders, as well as cancer, kidney, and nervous disorders. The bioavailability of a
drug can be improved with the use of solid lipid nanoparticles (SLNs) if it is not very water-soluble. The targeted
and controlled release of medications is another possible application. The objective of this research is to create
and assess bioactive SLNs derived from C. papaya seeds. Materials and Methods: The ripe, shade-dried papaya
seeds were first powdered and extracted using the Soxhlet method to obtain crude extract. Glycosides, alkaloids,
tannins, saponins, phenols, and flavonoids were all assessed during the phytochemical examination. The SLNs
of extract were formulated by a solvent evaporation method using Stearic acid as lipid and poloxamer 188 as
surfactant. Several of characteristics were used to assess the prepared SLNs, including encapsulation efficiency,
in vitro dissolution studies, zeta potential, particle size, and transmission electron microscopy (TEM). Chemical
confirmation of the produced SLNs was achieved using Fourier transform infra-red (FT-IR) and powder X-ray
diffractometry (XRD) analyses. The thermal stability of SLNs was studied with the help of differential scanning
calorimetry (DSC). Results and Discussion: The improved formulation had a zeta potential of −28.4 mV and a
polydispersity index of 0.021, and its particle size was determined to be 124.1 ± 22.3 nm. The effectiveness of
drug encapsulation was determined to be 80.98 ± 1.59. Formation of SLN confirmed by TEM, FT-IR analysis,
powder XRD, and DSC showed no unwanted peaks. The thermal stability of SLN was analyzed with the help
of DSC. An in vitro drug release study showed 89.30 ± 0.55% release of the drug in 12 h. Conclusion: The
evaluation results indicate an effective SLN formulation that might be used for antidiabetic effect.