Entecavir-loaded poly (lactic-co-glycolic acid) microspheres for long-term therapy of chronic hepatitis-B: Preparation and in vitro and in vivo evaluation.

To avoid severe exacerbations in the load of hepatitis B virus (HBV) as a consequence of discontinuous use of anti-HBV drugs, entecavir (ETV), the first-line anti-HBV drug, was primally formulated as extended-release poly (lactic-co-glycolic acid) microspheres in the present study. Because ETV is slightly soluble in water and in some other organic solvents used for microsphere preparation, methods for solid-microencapsulation were employed to fabricate the ETV microspheres. The optimized microspheres were evaluated for their morphology, particle size, drug loading, in vitro drug release, and in vivo pharmacokinetics in rats. The optimized formulation was found to have a mean particle size of 86 µm and drug loading of 13%. Differential scanning calorimetry and powder X-ray diffraction indicated that ETV existed in crystal, amorphous, and molecular states in the microspheres. In vitro and in vivo release revealed that the dissolution of ETV dominated the release process. The morphology of the microspheres and changes in the morphology during in vitro release were assessed by scanning electron microscopy. The novel ETV-MS described in this study should have great potential for clinical use as an alternative treatment against HBV.

A novel dendrimer-based complex co-modified with cyclic RGD hexapeptide and penetratin for noninvasive targeting and penetration of the ocular posterior segment.

Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15-20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvß3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p < .001), and modification extended retinal retention time for more than 12 h. Therefore, these NCs appear to be a promising noninvasive ocular drug delivery system for ocular posterior segment diseases.

Characterization and interfacial behavior of nanoparticles prepared from amphiphilic hydrolysates of ß-conglycinin-dextran conjugates.

Amphiphilic graft copolymers were prepared from ß-conglycinin-dextran conjugates hydrolyzed by trypsin at a degree of hydrolysis (DH) of 2.2%. Nanoparticles were prepared from ß-conglycinin, ß-conglycinin-dextran conjugates (CDC), and amphiphilic hydrolysates of ß-conglycinin-dextran conjugates at DH 2.2% (CDCH) by a desolvation method. All of the nanoparticle samples exhibited spherical structures, as evidenced by dynamic light scattering, transmission electron microscopy, and small-angle X-ray scattering. The nanoparticles prepared from amphiphilic hydrolysates of ß-conglycinin-dextran conjugates at DH 2.2% (CDCHN) exhibited higher interfacial pressure and dilatational modulus after long-term absorption at the oil-water interface compared with nanoparticles prepared from ß-conglycinin (CN) and ß-conglycinin-dextran conjugates (CDCN). This might be mainly associated with the higher surface hydrophobicity of CDCHN, which enhanced adsorption and intermolecular interactions of nanoparticles in the adsorbed layer.