Wilsonneal6691

The clinical efficacy of the PEGylated doxorubicin liposomes (PLD) is limited by low tumor accumulation and limited intra-tumoral disposition. Decoration with the cell penetration enhancers (CPEs) can increase the PLD permeability via the biological barriers, however at the expense of enhanced distribution to the non-target organs and tissues, and may interfere with their tumor accumulation and with the resulting anti-cancer effects. We investigated the effect of the surface CPE agent tetraArg-[G-1]-distearoyl glycerol (DAG-Arg4) on the systemic and intra-tumoral accumulation of PLD, using a 4 T1-Luc murine orthotopic model of breast cancer, using several analytical approaches. CPE-decorated liposomes undergo efficient in vitro endocytosis, and delivered doxorubicin to the cell nuclei. In vivo, they had lower tumor and spleen accumulation, similar liver accumulation, and higher lung accumulation, as compared to those of the PLD. Despite the lower tumor accumulation, CPE-decorated liposomes induced more prominent in vivo anti-cancer effects, as compared to the PLD, apparently ascribable to the higher intra-tumoral permeability mediated by the CPE surface residues. PFI2 Overall, liposomes decoration with the CPE residues had mostly beneficial effects on their systemic and intra-tumoral disposition. The mechanisms of the CPE-mediated effects on the liposome disposition should be further assessed with additional experimental models using robust analytical methods with high spatial resolution.The purpose of this study was to compare two types of emulsification techniques in a solid self-nanoemulsifying drug delivery system (SNEDDS); high-pressure homogenisation (HPH) and Shirasu porous glass membrane (SPG). Those two emulsification processes enhanced the solubility, dissolution and oral bioavailability of poorly water-soluble sildenafil base (SB) by producing fine and well-dispersed nanoemulsion droplet. The liquid SNEDDS consisting of Labrasol/Transcutol HP/coconut oil at the weight of 72/18/10, gave the smallest emulsion droplet size among the prepared liquid SNEDDS formulations. Then, the SB-loaded liquid SNEDDS was dissolved in the deionised water and applied to HPH or SPG techniques. Aerosil 200 was suspended as a mesoporous carrier and spray-dried, producing an SB-loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of each emulsification process were compared to the solid SNEDDS fabricated without any treatment of additional emulsification. Moreover, the physicochemical properties of all formulations were compared. The crystalline state of the drug in all products was converted to the amorphous state. The solid SNEDDS, subjected to HPH technique, provided fine and well-dispersed nanoemulsion. Additionally, it increasingly improved the drug solubility and dissolution as compared to the others, including SB powder, non-treated (NT) and SPG. Furthermore, it gave improved Cmax and increased AUC compared to SB powder and SPG, indicating HPH enhanced the oral bioavailability of SB the most. Thus, this solid SNEDDS with HPH would be strongly suggested as an oral SB-loaded pharmaceutical product.The purpose of this study was to develop a precursor liposome nano-delivery system for liquiritin (LT) to improve its solubility, oral bioavailability, and efficacy. The characterizations of the particle diameter, zeta potential, polydispersity index (PDI), droplet morphology, drug release in vitro, and oral bioavailability of the prepared LT precursor liposomes (LTMs) were carried out. In addition, streptozotocin intraperitoneal injection successfully induced diabetic mouse model, while the LT hypoglycemic effect, oral glucose tolerance, biochemical parameters and pathological sections were studied. The prepared LTMs were diluted to obtain a clear and transparent solution with a diameter of 91.84 ± 1.85 nm, zeta potential of -38.59 ± 2.65 mV and PDI of 0.215 ± 0.016. The in vitro release of the LTMs was superior to that of the free LT suspension, which may be related to the increased solubility of LT, as well as the small diameter and increased surface area. The obtained pharmacokinetic parameters indicated that the relative oral bioavailability of LTMs was increased by 8.8 times compared with the free LT suspension. Pharmacodynamic studies showed that LTMs effectively improved LT's hypoglycemic effect and diabetes-related organ repair, simultaneously confirmed its antioxidant activity. These results implied that the LTMs was an effective method to improve the solubility, oral bioavailability, and hypoglycemic activity of LT.Roll compaction/dry granulation often results in loss of tabletability. The two main hypotheses for this are granule hardening and granule size enlargement. The aim of this study was to investigate the effect of granule size, roll compaction force, and granule fragmentation upon tableting and its effect on tabletability of granules constituting a ductile or brittle material. Plastically deforming microcrystalline cellulose (MCC) and fragmenting lactose monohydrate (lactose) were roll compacted at five roll compaction forces ranging from 2 to 16 kN/cm. Granule size fractions of 250-355 and 500-710 µm were blended with 10% magnesium stearate (MgSt), compressed into tablets and ground to obtain compressed granules. The predominant deformation behaviour of the particles constituting the granules directly impacted granule deformation upon tableting, as lactose granules fractured extensively upon tableting, whereas MCC granules predominantly deformed by plastic deformation. Increased roll compaction force resulted in more granule hardening of both materials and thereby granules less susceptible to fragmentation upon tableting. Granule hardening accounted for the largest loss of tabletability of MCC granules upon roll compaction. Roll compaction force and granule size had no or negligible effect on tabletability of lactose tablets without MgSt, whereas increased roll compaction force and larger granules decreased tensile strength of tablets containing lactose granules blended with MgSt. This was explained by inter-particle and inter-granular bonds contributing equally to the tensile strength of lactose tablets without MgSt. However, after addition of MgSt, the decreased fragmentation tendency of larger granules compacted at higher roll compaction forces resulted in greater MgSt coverage of the granules upon tableting, thereby decreasing tabletability.