Abstract
The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.
Highlights
Cisplatin (CP) is a main chemotherapeutic treatment that has been used against different types of solid malignant tumors, i.e., testicular germ cell tumor (TGCT) [1]
The current study provides evidence for the promising ameliorative effects of Self-nanoemulsifying self-nanosuspension (SNESNS) on gonadotoxicity induced by CP
The design of an nutraceutical formulation (NCF) with SNESNS has been applied to mitigate or minimize CP-induced spermatotoxicy. This is the first design of a unique formulation of three variable nutraceutical origins with different physical character in a homogenous stable SNESNS drug delivery system, and each 1 g of the prepared formula is composed of 250 mg SP which is blue-green algae, 100 mg fish oil (FO) which is of fish source, and Terrestris L. (TT) as a dried herb extract using Span 80/cremophor EL as surfactant and isopropanol as cosurfactant in the establishment of self-nanoemulsifying drug delivery systems (SNEDDS) with FO in the percentage of (30% FO; 50% span80/cremophor EL; 20% isopropanol)
Summary
Cisplatin (CP) is a main chemotherapeutic treatment that has been used against different types of solid malignant tumors, i.e., testicular germ cell tumor (TGCT) [1]. (TT), family Zygophyllaceae, is a shrub, growing in subtropical climates all over the world [7] It consists of numerous biologically active constituents like steroidal saponins, unsaturated fatty acids, alkaloids, flavonoids, tannins, and vitamins. TT was found to induce powerful protection against cadmium-induced testicular toxicity through retardation of testicular peroxidation by antioxidant and metal chelating activity and maybe indirectly by stimulating the production of testosterone from Leydig cells [9]. No studies have been performed on the use of the combination of these three constituents This stimulated our consideration to investigate the potential protective and/or recovery of TT, FO, and SP extracts separately and simultaneously in a novel nano-sized formulation for CP-induced testicular toxicity in male rats. Several parameters have been evaluated for biological investigation, including spermatological changes, testicular histopathological alterations, hormonal changes, oxidative stress parameters, inflammatory markers, and apoptotic status
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