New method and characterization of self-assembled gelatin-oleic nanoparticles using a desolvation method via carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction.

In this study, we investigated a new method for the preparation of gelatin-oleic conjugate (GOC) as an amphiphilic biomaterial to load model anti-cancer drugs into self-assembled nanoparticles (NPs). Oleic acid (OA) was covalently bound to gelatin via carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction in water-ethanol cosolvent to form a GOC. Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance ((1)H NMR) clearly indicated the successful synthesis of GOC. The percentage of gelatin amino groups reacted with OA was up to 50% as determined using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) method. Subsequently, gelatin-oleic nanoparticles (GONs) were prepared using a desolvation method with glutaraldehyde or genipin used as a crosslinker for comparison. Irinotecan hydrochloride (IRT) was used as a model drug to load into GONs using incubation or an in-process adding method for comparison. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) data showed that the sizes of GONs and IRT-loaded GONs (IRT-GONs) were below 250 nm. The zeta potentials of the GONs and irinotecan-loaded IRT-GONs were below -20 mV, which was found to be stable in suspension against the aggregation process. The incubation method was more suitable for drug loading because it did not affect the process of GON formation and thus did not increase their size much compared to the change in size with the in-process adding method. The lipophilic property of the oleic moiety in the GOC increased the affinity between GOC molecules, thus reducing the amount of crosslinking agents needed to stabilize GONs compared to gelatin nanoparticles (GNs). As novel approaches for the synthesis of protein-fatty acid complexes, chemical reaction has been suggested for the synthesis of GOC. The above results show that GOC synthesized via new method is a promising biomaterial based upon preparation of nanoparticles.

Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs.

Over 40% of active pharmaceutical ingredients (API) in development pipelines are poorly water-soluble drugs which limit formulation approaches, clinical application and marketability because of their low dissolution and bioavailability. Solid dispersion has been considered one of the major advancements in overcoming these issues with several successfully marketed products. A number of key references that describe state-of-the-art technologies have been collected in this review, which addresses various pharmaceutical strategies and future visions for the solubilization of poorly water-soluble drugs according to the four generations of solid dispersions. This article reviews critical aspects and recent advances in formulation, preparation and characterization of solid dispersions as well as in-depth pharmaceutical solutions to overcome some problems and issues that limit the development and marketability of solid dispersion products.

Novel multifunctional biocompatible gelatin-oleic acid conjugate: self-assembled nanoparticles for drug delivery.

In this work, a novel, biocompatible conjugates of gelatin and oleic acid (GOC) were synthesized by a novel aqueous solvent-based method that overcame challenges of completely contrary solubility between gelatin and oleic acid (OA). The GO nanoparticles (GONs) and Paclitaxel encapsulated nanoparticles (PTX-GON) were prepared by self-assembly in water. These nanoparticles (NPs) were then conjugated with folic acid (FA) for targeting cervical cancer cells (Hela cells) and were characterized for their various physicochemical and pharmaceutical properties. Fourier transform infrared spectroscopy (FT-IR) and 1H NMR studies indicated the successful synthesis of GOC which showed low critical aggregation concentration in water (0.015 mg/ml). All NPs were stable in human blood serum and their mean diameters were below 300 nm suitable for passive targeting. Powder X-ray diffraction (PXRD) diffractograms showed the reduction in drug crystallinity and hence, leading to the solubility enhancement of PTX. The release of PTX from both PTX-GON and FA conjugated PTX-GON (PTX-FA-GON) was controlled for a long time. The cytotoxicity results demonstrated great advantages of PTX-FA-GON and PTX-GON over the conventional dosage form of pacliaxel (Taxol). These results, therefore, indicate that GOC is a promising material to prepare drug encapsulated NP as a controlled delivery system and PTX-FA-GON is a potential targeted delivery system for cancer therapy.