Oligoalanine-modified Pluronic-F127 nanocarriers for the delivery of curcumin with enhanced entrapment efficiency

Abstract

Curcumin is a naturally occurring compound that has been shown to have anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. However, its pharmaceutical potential has been limited due to its low solubility in water. The use of amphiphilic nanocarriers is an attractive and simple method to solubilize curcumin. In this study, we modified Pluronic F-127 [poly(ethylene glycol)100-block-poly(propylene glycol)65-block-poly(ethylene glycol)100] (PF-127) with oligomers of alanine, an amino acid, to increase the drug entrapment efficiency of curcumin through core stabilization. Alanine-modified PF-127 exhibited lower critical micelle concentration and decreased molecular motion in both the hydrophilic and hydrophobic segments ((1)H NMR). Nanocarriers in the size range of 54.2-68.4 nm were observed. Entrapment efficiency of curcumin increased by at most 66% (from 25.3 to 91.3%) and the difference in solubility was clearly visualized by increased transparency of the nanocarrier solutions. Curcumin was released continuously up to 120 h from modified carriers, while drug release from unmodified carriers plateaued within 24 h. These modified nanocarriers exhibited no cytotoxicity and more efficiently delivered drugs to HeLa cells as confirmed by fluorescent microscopy. This study demonstrated that alanine modification of FDA-approved PF-127 affects copolymer nanoassembly and has a profound impact on curcumin loading and possibly on other hydrophobic drugs as well.

Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery

“…These nanocarriers are very promising systems for target-specific delivery of drugs, because they have high drug loading (DL) capacity and enhanced cellular uptake efficiency − with the ability to protect the drug and postpone its degradation. , Recent advances deal with the development of stimuli-responsive polymeric hydrogels. , For this aim, thermoresponsive-triblock copolymers such as Pluronic (PEO–PPO–PEO) has extensively been studied, especially in drug delivery due to their approved use in medical devices by the US Food and Drug Administration . The self-assembly of amphiphilic copolymers through hydrophobic interactions of poly­(propylene oxide) (PPO) blocks in the inner core and hydrophilic interactions of poly­(ethylene oxide) (PEO) blocks in the outer shell forms water soluble micelles above the lower critical solution temperature . Hydrophobic drugs can easily be loaded inside the micelles to improve their therapeutic activity, metabolic stability, and circulation time .…”

“…Although the drug has a wide range of pharmacological effects such as anti-inflammatory, antioxidant, antimutagenic, and antitumor properties, its application in treatments of many diseases is confined due to low solubility in aqueous solutions and rapid degradation at physiological pH . Therefore, encapsulation of the drug in the nanocarriers is an effective method for efficient anticancer treatment, owning to the presence of large hydrophobic blocks in Pluronic, as a cargo space. , For instance, Sahu et al showed that the encapsulation yield of curcumin-loaded Pluronic micelles can be tuned with the drug to polymer ratio. Nevertheless, the copolymers suffer from dissociation upon dilution, owing to the relatively high critical micelle concentration (CMC) .…”

Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: pharmaceutical, biological, and toxicological studies

“…Recent pharmaceutical research had focused on phytomedicine. 6,7 Numerous medicinal plants possessing profound central nervous system (CNS) effects and antioxidant activity have recently received attention to improve cognitive function in AD. Piperine (PIP) (1-piperoylpiperidine) is a nitrogenous pungent alkaloid present in the fruits of black pepper (Piper nigrum), long pepper (Piper longum), and other piper species (family: Piperaceae).…”

Physicochemical Properties and Control Release of Aloe Vera (Aloe barbadensis Miller) Bioactive Loaded Poly (Lactic Co-Glycolide Acid) Synthesized Nanoparticles

“…An EE of 47.6% and 38.9% for cinnamon bark extract loaded in PLGA-50 and PLGA-65 NP, respectively was reported by Hill et al [18]. Peng et al [19] also reported about 80% time release of plant oil curcumin encapsulated with PF127 micelles during 6-h period at 37˚C. The control release of active compounds is govern by Fick's law of diffusion, when a species of bioactive entrapped at specific site (initial position) migrates through a polymeric a matrix to the surface and subsequent release into the medium surrounding the NP [20], hence influenced the concentration differences combined with electrokinectic and other physical properties.…”