Nano Encapsulated Curcumin: And Its Potential for Biomedical Applications

Figures & data

Figure 1 Chemical structures of (A) curcumin, (B) demethoxycurcumin and (C) bisdemethoxycurcumin.

Figure 2 The uptake of F-CUR-L through folate receptor-mediated endocytosis pathway.

Figure 3 Schematic representation of pH-triggered release of IM-Chol liposomes. Reprinted from Int J Pharm. 518. Ju L, Cailin F, Wenlan W, et al. Preparation and properties evaluation of a novel pH-sensitive liposomes based on imidazole-modified cholesterol derivatives, 213–219, Copyright 2017, with permission from Elsevier.⁴²

Table 1 Different Types of Cur-Loaded Polymeric Micelles

Types of Micelles	Composition	Preparation Methods	Major Outcome	References
Normal micelles	MPEG-PCL	Solid dispersion method	Improved water solubility Inhibition of breast tumor growth and spontaneous pulmonary metastasis	[^Citation51]
EGFR-targeted micelles	PLGA-PEG GE11 peptides	Emulsification solvent evaporation method	Increased intracellular uptake Prolonged circulation A reduction in primary tumor burden	[^Citation58]
FR-targeted micelles	Folate-PEG3000-PLA2000 mPEG2000-PLA2000	Thin film-hydration method	Increased intracellular uptake Sustained drug release Improved solubility Cancer targeting Enhanced anti-cancer activity	[^Citation13]
pH-sensitive micelles	TPGS-PAE	Solvent evaporation method	Low polydispersity High encapsulation efficiency Enhanced release in the acidic environment Improved pro-apoptotic and antiangiogenic activities	[^Citation60]
Redox-sensitive micelles	C16-SS-CS-mPEG	Dialysis method	Controlled drug release Enhanced antitumor and anti-inflammation efficacy	[^Citation61]

Figure 4 In vitro release profiles of (A) Dox and (B) Cur from D + C/NPs at pH 7.4 or 5.8. Reprinted from Acta Biomater. 58. Zhang J, Li J, Shi Z, et al. pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities, 349–364, Copyright 2017, with permission from Elsevier.⁶⁰

Figure 5 Chemical structures of (A) C₁₆-SS-CS-mPEG and (B) C₁₆-CC-CS-mPEG.

Figure 6 Schematic representation comparing cytotoxic effect of (A) pure curcumin and (B) curcumin loaded MCM-41on SCC-25 cells. MCM-41-CUR was achieved via hydrogen-bond interaction and showed higher cytotoxicity. Reprinted from RSC Adv. 4. Jambhrunkar S, Karmakar S, Popat A, et al. Mesoporous silica nanoparticles enhance the cytotoxicity of curcumin, 709–712, Copyright 2014, with permission from The Royal Society of Chemistry.⁹⁶

Figure 7 Chemical structures of most frequently used cyclodextrins.

Table 2 Preparation Methods of Cur-Loaded Nanocrystals

Types of Preparation Methods	Preparation Methods	Particle Size (nm)	Stabilizers	References
Top-down	High-pressure homogenization method	500–800	PVA, PVP, TPGS, sodium carboxyl methyl cellulose (Na-CMC) or sodium dodecyl sulfate (SDS)	[^Citation163]
	Grinding method	250	Hydroxypropyl cellulose SL (HPC-SL) and SDS	[^Citation164]
	Grinding and high-pressure homogenization method	181	Stabilizer solution	[^Citation165]
Bottom-up	Precipitation method	104 or 135	Sodium lauryl sulfate or poloxamer 188	[^Citation166]
	Thin-film dispersion method	161.9	Pluronic F127	[^Citation167]

Figure 8 Characterization of formulations. (A) Appearances of free Cur, Cur-NCs, and HA@Cur-NCs. TEM images of (B) Cur-NCs and (C) HA@Cur-NCs. Reprinted from Biomater Sci. Ji P, Wang L, Chen Y, et al. Hyaluronic acid hydrophilic surface rehabilitating curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution, 462-472. Copyright 2020, with permission from The Royal Society of Chemistry.¹⁶⁷

Table 3 Examples of Cur-Loaded Nanoformulations for Treatment of Different Diseases

Disease	Cur-Loaded Nanoformulation	Animal	Major Outcome	References
Cancer	MPEG-PCL micelles	BALB/c mice	Sustained drug release Enhanced anti-cancer efficacy Improved anti-metastasis activity	[^Citation51]
Brain injury	PLGA nanoparticles	Sprague Dawley rats	Down-regulated expression of NF-κB Decreased early brain injury induced by subarachnoid hemorrhage	[^Citation168]
	PLGA nanoparticles	Sprague Dawley rats	Improved neurological deficit Attenuated brain edema Enhanced therapeutic potential against subarachnoid hemorrhage- induced blood-brain barrier disruption	[^Citation169]
Wound healing	Dextran hydrogel incorporated PEG–PLA micelles	BALB/c mice	Acceptable biocompatibility Accelerated angiogenesis, fibroblast accumulation and wound healing	[^Citation170]
	PVA/Chitosan/ Curcumin patches	Albino wistar rats	Increased bioavailability Improved anti-bacterial activity Enhanced wound healing	[^Citation171]
Malaria	PLGA nanoparticles	C57BL/6 mice	Enhanced and delayed uptake in the brain. Preventing degenerative changes in cerebral malaria	[^Citation172]
	PLGA nanoparticles	Swiss male albino mice	Higher potency against malaria parasite Higher safety	[^Citation173]
Asthma	Solid lipid nanoparticles	BALB/c mice Sprague Dawley rats	Enhanced bioavailability Increased tissue concentrations Suppressed airway hyperresponsiveness and inflammatory cell infiltration	[^Citation174]
Psoriasis	Hydrogel coated PLGA nanoparticles	C57/BL6 mice	Enhanced topical penetration and system exposure Improved anti-psoriasis activity	[^Citation175]
Arteriosclerosis	MPEG-PCL micelles	ApoE^−/- mice	Inhibition of intraplaque neovascularization Reduced matrix metalloproteinases 2/9 activity and inflammatory response Regulation of lipoprotein cholesterol metabolism	[^Citation176]
Leishmaniasis	Chitosan nanoparticles	Male albino rats	Satisfactory loading efficiency, stability and drug release characteristics Higher anti-leishmaniasis efficiency	[^Citation177]
Bacterial infection	PVP nanoparticles	C57BL/6 mice	Improved anti-bacterial and anti-inflammatory effects Enhanced therapeutic potency of vancomycin	[^Citation178]

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