SN-38 loaded polymeric micelles to enhance cancer therapy

Abstract

7-Ethyl-10-hydroxycamptothecin (SN-38) loaded poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (Pluronic F-108) and poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nanoparticles were successfully prepared by a modified film hydration method and characterized by scanning electric microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). Satisfactory drug loading of 20.73 ± 0.66% and a high encapsulation efficiency of 83.83 ± 1.32% were achieved. The SN-38 nanoparticles (SN-38 NPs) can completely disperse into a phosphate buffered saline (PBS) medium to produce a clear aqueous suspension that remains stable for up to three days. Total drug releases were 67.91% and 91.09% after 24 h in a PBS or fetal bovine serum (FBS) medium. Half maximal inhibitory concentration (IC(50)) tests of SN-38 and SN-38 NPs on A549 lung cells produced results of 200.0 ± 14.9 ng ml(-1) and 80.0 ± 4.6 ng ml(-1), respectively. Similarly, IC(50) tests of SN-38 and SN-38 NPs on MCF-7 breast cells yielded results of 16.0 ± 0.7 ng ml(-1) and 8.0 ± 0.5 ng ml(-1), respectively. These in vitro IC(50) studies show significant (p < 0.01) enhancement of the SN-38 NP drug efficiency in killing cancer cells in comparison to the free drug SN-38 control. All the materials used for this nanoformulation are approved by the US FDA, with the virtue of extremely low toxicity to normal cells.

Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38

“…Drug loading of Pluronic F-108/PEG-b-PCL micelles was significantly higher than CS-g-PCL or mPEG-SS-PBLG micelles, which might indicate the advantage of using a second more hydrophobic copolymer (which swells the core and improves drug solubility in the core) without compromising particle size and entrapment efficiency [89][90][91]. The micelles displayed prolonged release of SN38 in PBS, which might be the reason for the lower cytotoxicity of the micelles in Table 3 The physicochemical properties of film hydrated (FH) and film loaded (FL) liposomes.…”

“…comparison with free SN38 in cell viability studies [89][90][91]. Further comprehensive animal studies allowing the evaluation of the prolonged circulation of the micelles in directing the therapeutic effect are required to fully establish the suitability of those formulations in the clinic.…”

“…Table 4 The physicochemical properties and % of drug release of different SN38-loaded polymeric micelles (reproduced from Refs. [89][90][91] Abbreviations: PS = particle size, CMC = critical micellar concentration, DL = % of the mass of loaded drug divided by the mass of polymeric micelles, EE = entrapment efficiency. a See comment in text regarding the release data for SN38 using dialysis -the authors of the current review doubt that these release kinetics reflect the true release rate from selfassembled micelles.…”

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

“…Several approaches to overcome the problem of SN-38 solubility and stability have been proposed, including incorporation into nanoparticles (2,4,5), liposomes (6), and polymeric micelles (7)(8)(9), conjugating with water-soluble polymers like polyethylene glycol (10), PAMAM dendrimers (11), peptides (1), carbohydrates (12), etc. All these approaches involve tedious processing or synthetic steps and expert skills and industrialization or scale-up is also an important problem.…”

Novel Dexamethasone-Loaded Nanomicelles for the Intermediate and Posterior Segment Uveitis

“…Nanocarriers such as liposomes and nanomicelles are capable of solubilizing highly hydrophobic drugs in aqueous medium (11)(12)(13)(14). Micelles represent supramolecular Electronic supplementary material The online version of this article (doi:10.1208/s12249-014-0100-4) contains supplementary material, which is available to authorized users.…”