Encapsulated Phytomedicines against Cancer: Overcoming the "Valley of Death".

P2Et is the standardized extract of Caesalpinia spinosa (C. spinosa), which has shown the ability to reduce primary tumors and metastasis in animal models of cancer, by mechanisms involving the increase in intracellular Ca++, reticulum stress, induction of autophagy, and subsequent activation of the immune system. Although P2Et has been shown to be safe in healthy individuals, the biological activity and bioavailability can be increased by improving the dosage form. This study investigates the potential of a casein nanoparticle for oral administration of P2Et and its impact on treatment efficacy in a mouse model of breast cancer with orthotopically transplanted 4T1 cells. Animals were treated with either free or encapsulated oral P2Et orally or i.p. Tumor growth and macrometastases were evaluated. All P2Et treatments significantly delayed tumor growth. The frequency of macrometastasis was reduced by 1.1 times with P2Et i.p., while oral P2Et reduced it by 3.2 times and nanoencapsulation reduced it by 3.57 times. This suggests that nanoencapsulation led to higher doses of effective P2Et being delivered, slightly improving bioavailability and biological activity. Therefore, the results of this study provide evidence to consider P2Et as a potential adjuvant in the treatment of cancer, while the nanoencapsulation of P2Et provides a novel perspective on the delivery of these functional ingredients.

Conformational Behavior, Topographical Features, and Antioxidant Activity of Partly De-Esterified Arabinoxylans.

This study aimed to investigate the effect of arabinoxylans (AX) partial de-esterification with feruloyl esterase on the polysaccharide conformational behavior, topographical features, and antioxidant activity. After enzyme treatment, the ferulic acid (FA) content in AX was reduced from 7.30 to 5.48 µg FA/mg polysaccharide, and the molecule registered a small reduction in radius of gyration (RG), hydrodynamic radius (Rh), characteristic ratio (C∞), and persistence length (q). A slight decrease in α and a small increase in K constants in the Mark-Houwink-Sakurada equation for partially de-esterified AX (FAX) suggested a reduction in molecule structural rigidity and a more expanded coil conformation, respectively, in relation to AX. Fourier transform infrared spectroscopy spectra of AX and FAX presented a pattern characteristic for this polysaccharide. Atomic force microscopy topographic analysis of FAX showed a more regular surface without larger hollows in relation to AX. The antioxidant activity of FAX, compared to AX, was reduced by 30 and 41% using both 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) methods, respectively. These results suggest that feruloyl esterase treatment of AX could offer a strategy to tailor AX chains conformation, morphological features, and antioxidant activity, impacting the development of advanced biomaterials for biomedical and pharmaceutical applications.

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery.

Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

Maize arabinoxylan gels as protein delivery matrices.

The laccase induced gelation of maize bran arabinoxylans at 2.5% (w/v) in the presence of insulin or beta-lactoglobulin at 0.1% (w/v) was investigated. Insulin and beta-lacto-globulin did not modify either the gel elasticity (9 Pa) or the cross-links content (0.03 and 0.015 microg di- and triferulic acids/mg arabinoxylan, respectively). The protein release capability of the gel was also investigated. The rate of protein release from gels was dependent on the protein molecular weight. The apparent diffusion coefficient was 0.99 x 10(-7) and 0.79 x 10(-7) cm(2)/s for insulin (5 kDa) and beta-lactoglobulin (18 kDa), respectively. The results suggest that maize bran arabinoxylan gels can be potential candidates for the controlled release of proteins.