Polymeric curcumin nanoparticles by a facile in situ method for macrophage targeted delivery

Abstract

Targeting macrophages is a promising strategy for improved therapy of intracellular infections as macrophages exhibit rapid phagocytosis of particles >200 nm. Entrapment of Curcumin (CUR) in nanocarriers could provide bioenhancement and macrophage targeting. We present a simple and facile in situ nanoprecipitation approach for instantaneous and on-site generation of curcumin nanoparticles (ISCurNP). ISCurNP optimised by Box-Behnken design exhibited average size of 208.25 AE 7.55 nm and entrapment efficiency of 90.16 AE 1.17%. Differential scanning calorimetry and X-Ray diffraction confirmed amorphization of CUR in ISCurNP. Sustained release was observed over 72 hr in vitro at lysosomal pH 4.5. Rapid and high uptake in RAW 264.7 macrophages was confirmed by flow cytometry and high performance liquid chromatography. Confocal microscopy established localisation of ISCurNP in lysosomal compartment. The facile in situ nanoprecipitation method provides simple, scalable technology to enable macrophage targeted delivery of CUR, with great promise for improved therapy of intracellular infections. K E Y W O R D SCurcumin, in situ, nanoparticles, macrophages, nanoprecipitation, intracellular uptake, Box Behnken 1 | INTRODUCTION Curcumin (CUR), a natural polyphenol has generated tremendous excitement as a nutraceutical due to its multifarious pharmacological activities.1,2 The anticancer 3-6 and anti-inflammatory 7,8 properties of CUR have been widely explored. CUR, an established anti-infective for eons, is currently being extensively researched for antibacterial including antimycobacterial, antiviral, and antifungal activity. 9-11Despite the excellent therapeutic potential, a considerable impediment in exploitation of CUR as a therapeutic agent is its hydrophobic nature and consequently poor aqueous solubility. 12Nanonization of particles has proven to be a competent approach to enhance solubility and bioavailability of hydrophobic poorly soluble drugs. 13,14 Furthermore, such drugs when entrapped in nanocarriers with size titrated in the range of 200-600 nm can aid targeting to the reticuloendothelial system (RES) organs and cells, especially macrophages, the primary site of various intracellular infections. 15-18Macrophages constitute defense system of the body and exhibit rapid phagocytosis of particles >200 nm. | ISCurNPPreconcentrates were added to filtered distilled water for instantaneous formation ISCurNP. | Optimization of ISCurNP 2.4.1 | Preliminary screeningPreliminary screening was carried out using the one variable at a time | Design of experiment: Box-Behnken designISCurNP was optimized by applying Box-Behnken design. Independent variables selected were concentration of Soluplus ® (X1), concentration of PLGA (X2), and volume of DMA (X3) in the preconcentrate and the dependent variables (responses) were particle size (PS; Y1), and percent entrapment efficiency (%EE; Y2) of the generated ISCurNP. Curcumin concentration (10 mg) and aqueous dilution volume (10 ml) were maintained constant. The indepen...

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

“…Curcumin is an active principle with multiple pharmacological activities, but its high hydrophobicity restricts its aqueous solubility and applicability [ 218 , 219 , 220 ]. Curcumin encapsulated in PLGA nanoparticles has been explored as a new strategy to improve the intracellular delivery of this active principle to improve antibacterial, antiviral, antimycobacterial and antifungal properties [ 8 ]. PLGA-curcumin PNs were more efficiently phagocyted by macrophages as compared to free curcumin, demonstrating the potential of this nanoplatform to fight intracellular infections.…”

“…Encapsulation of drugs into nanoparticles (NP) represents a valuable option to improve drug solubility and biodistribution, prevent undesirable interactions and drug degradation before reaching the target tissues and cells [ 1 ] and non-specific accumulation of drugs in other tissues. In this context, nanoencapsulated drugs hold the potential to increase the efficiency and effectiveness of therapeutic regimens, particularly in drugs with low solubility, short half-life, variable absorption, and undesirable interactions [ 4 , 7 , 8 , 9 , 10 , 11 , 12 ]. Such improvement comes from the reduction of dose and drug frequencies in patients, which dramatically impact on decreasing both toxic and side effects that drugs usually have intrinsically.…”

“…In recent years, a large number of drug delivery systems have been described in many medical areas, including intracellular infections [ 3 , 5 , 7 , 8 , 10 , 18 , 29 , 30 , 33 ]. Indeed, the global infectious disease therapeutics market size was valued at $46.88 billion in 2018 and is estimated to reach $64.5 in 2023 [ 34 ].…”

Recent developments in formulation design for improving oral bioavailability of curcumin: A review

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Curcumin-incorporated Thiolated Chitosan/alginate Nanocarriers: Physicochemical Properties and Release Mechanism

“…The thermal properties and molecular dispersion of curcumin, blank NPs, and curcumin-loaded NPs were examined using differential scanning calorimetry (DSC, Perkin Elmer DSC 8000, Waltham, MA, USA). Accurately weighed samples in a solid pan were placed in the instrument with temperature programmed from 20-250 o , rate 10°/min [16,17] . Scanning electron microscope (SEM, Tescan Mira 3, Czech Republic) was performed to analyse the morphological characteristics of the NPs.…”