New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

PEGylated Doxorubicin Prodrug-Forming Reduction-Sensitive Micelles With High Drug Loading and Improved Anticancer Therapy

Significant efforts on the design and development of advanced drug delivery systems for targeted cancer chemotherapy continue to be a major challenge. Here, we reported a kind of reduction-responsive PEGylated doxorubicin (DOX) prodrug via the simple esterification and amidation reactions, which self-assembled into the biodegradable micelles in solutions. Since there was an obvious difference in the reduction potentials between the oxidizing extracellular milieu and the reducing intracellular fluids, these PEG–disulfide–DOX micelles were localized intracellularly and degraded rapidly by the stimulus to release the drugs once reaching the targeted tumors, which obviously enhanced the therapeutic efficacy with low side effects. Moreover, these reduction-sensitive micelles could also physically encapsulate the free DOX drug into the polymeric cargo, exhibiting a two-phase programmed drug release behavior. Consequently, it showed a potential to develop an intelligent and multifunctional chemotherapeutic payload transporter for the effective tumor therapy.

Delivery of Ursolic Acid by Polyhydroxybutyrate Nanoparticles for Cancer Therapy: in silico and in vitro Studies

Ursolic acid (UA), a pentacyclic triterpenoid and a phytochemical, is a potent inhibitory agent against proliferation of various tumors. Polyhydroxybutyrate nanoparticles (PHB NPs) are preferred in therapeutics due to their drug-stabilizing property and enhanced biological activity. In this study, PHB NPs were utilized to deliver and enhance the bioavailability of UA against cancer cells (HeLa). Further, molecular docking and dynamic studies were conducted to calculate the binding affinity and stability of UA at the active site of target protein (epidermal growth factor receptor-EGFR). The PHB NPs revealed the average size as 150–200 nm in TEM, which were used in subsequent experiments. The cytoplasmic uptake of nanoparticles was confirmed by florescent microscopy. The encapsulation potential of PHB NPs with UA was assessed by UV–visible spectrophotometer as 54%. Besides, the drug release behavior, cytotoxicity and the regulation of apoptosis were investigated in vitro. The cytotoxicity results revealed that the maximum efficiency of drug delivery was at 96th hour.

Hydrophilic Excipient-Independent Drug Release from SLA-Printed Pellets

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.

Heat Treatment Induced Specified Aggregation Morphology of Metoprolol Tartrate in Poly(ε-caprolactone) Matrix and the Drug Release Variation

Hot-melt blending has been widely used in the pharmaceutical industry to produce drug delivery systems, however, realizing the controlled drug release behavior of a hot-melt blended medicament it is still a tough challenge. In this study, we developed a simple and effective heat treatment method to adjust the drug release behavior, without the addition of any release modifiers. Thin metoprolol tartrate (MPT)/poly(ε-caprolactone) (PCL) tablets were prepared through hot-melt processing, and different morphologies of MPT were obtained by altering processing temperatures and the following heat treatment. MPT particles with different particle sizes were obtained under different processing temperatures, and fibrous crystals of MPT were fabricated during the following heat treatment. Different morphological structures of MPT adjusted the drug diffusion channel when immersed in phosphate-buffered saline (PBS), and various drug release behaviors were approached. After being immersed for 24 h, 7% of the MPT was released from the blend processed at 130 °C, while more than 95% of the MPT were released after the following heat treatment of the same sample. Thus, flexible drug release behaviors were achieved using this simple and effective processing manufacture, which is demonstrated to be of profound importance for biomedical applications.

Design and Fabrication of Photo-Responsive Hydrogel for the Application of Functional Contact Lens

Traditional hydrogel has usually had restricted application in the biomedical field due to lack of a control unit. Herein, Azobenzene (AZO), as a typical kind of photo-response molecule, was introduced into hydrogel by polymerization to provide a control unit for hydrogel. Simultaneously, the immobilization of AZO end group would solve the problems of uncontrollable recovery and light fatigue for AZO small molecules according to previous research. In the research, two kinds of crosslinkable AZO molecules, namely AZO crosslinker and AZO monomer, were synthesized as functional monomers or crosslinkers. Further, AZO copolymerized hydrogel and AZO crosslinked hydrogel were obtained. In order to estimate fundamental properties for contact lenses, gelation time and swelling ratio of hydrogels as a function of AZO concentration as well as crosslinking type were investigated. Moreover, synthesized hydrogels exhibited typical porous morphology, but their size and homogeneity were dependent on the type of hydrogel. In order to evaluate photo-responsive performance, detailed photo induced isomerization of both AZO copolymerized hydrogel and crosslinked hydrogel were tracked by UV spectra. The results confirmed the reversible, stable, and controllable photo responsive process. In vitro evaluation was used to investigate drug release behavior using orfloxacin and puerarin as model drugs. It was found that AZO addition as well as hydrogel type would influence puerarin release, but would have little effect on the orfloxacin release behavior in hydrogels. Furthermore, the isomer type in the hydrogel would have some effects on drug release behavior including orfloxacin and puerarin.