Objective: Ovarian cancer is the most deadly cancer in women, ranking fourth among all fatal diseases in women. Conventional chemotherapy has its own plethora of challenges, such as side effects and disease relapse. Hydroxyurea is a type of anticancer drug that is commonly used to treat malignancies. This study aims to develop and optimize hydroxyurea nanostructured lipid carriers (NLCs) to improve the therapeutic index and reduce its side effects in the effective treatment of OC.
Methods: NLCs were prepared by microemulsion technique. They were prepared and optimized using the design of experiment for particle size and drug entrapment efficiency. Particle size, polydispersity index, zeta potential, morphology, in vitro release, and stability were all examined in the optimized formulation.
Results: The results showed that the particle size of the NLCs was in the range of 224 nm to 634 nm. The drug entrapment efficiency of the NLCs was in the range of 46.33 % to 70.43 %. The optimized NLCs had a particle size of 237 nm, a polydispersity index of 26.9%, and a zeta potential of-29.7 mV. These NLCs were spherical, showed in vitro drug release of 92.21% up to 48 h, and were found to be stable from the stability studies.
Conclusion: This approach could be used as a better drug delivery platform to improve the drug's therapeutic index, reduce its side effects, and be feasible in the effective management of ovarian cancer.
Nanosponges are drug delivery systems consisting of nano-sized sponges incorporated with drug substances. Recently, this technology has advanced the management of many diseases which require targeted delivery. This technique can provide enhanced permeability owing to its size range. Curcumin-loaded nanosponges (CURNS) were prepared with the objective of enhancing their permeability. They were formulated by emulsion solvent diffusion method using minimum run screen design. By the initial trails, the constraints for independent variables, polymer concentration, and stirring speed were standardized and experimental runs were generated. The prepared nanosponges were characterized by scanning electron microscopy, micrometric properties, %yield, drug entrapment efficiency, in vitro release studies, in vitro release kinetics, and in vivo pharmacokinetics. According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) norms, accelerated stability experiments for the optimized formulation were conducted. The scanning electron microscope images prove that the particles are spherical, porous on their outer surface, and spongy. The average particle size of the optimized formulation was 166.3 ± 23.32 nm, suitable for oral delivery. The optimized formulation showed controlled release of the drug with enhanced release in the colon, indicating colon-specific release. Curve-fitting analysis followed the Higuchi model. Pharmacokinetics and biodistribution results of CURNS after oral administration in rabbits proved that CURNS showed a significantly different pharmacokinetic property than that of pure curcumin solution. AUC 0−t of CURNS (11.55 ± 1.123 μg/ml per minute) in plasma was around 3.07-fold greater than CUR solution (3.755 ± 0.985 μg/ml per minute), and the mean residence time (23.0118 ± 4.563 vs. 13.921 ± 5.653 hours) was 1.42-fold longer. These findings revealed that the bioavailability of curcumin was increased. Hence, nanosponges of curcumin were found to be more effective.
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