Table 2.

Characterization, target indications, drug release pattern, and cytotoxicity of albumin and functionalized albumin nanoparticles prepared by desolvation process

Albumin used	Functionalizing or conjugating agent	Drug or antioxidant loaded	Target indication	Outcome or application†	Reference
Egg albumin	–	Curcumin (CUR)	–	Particle diameter: 232 nm, DLC: 4.125%, DEE: 55% Enhanced solubility of CUR RSM was used for process optimization	[32]
HSA	–	Doxorubicin	Neuroblastoma (UKF-NB3 and IMR-32 cell lines)	Particle diameter: 158.5 nm, ZP: −31.9 mV, DEE: 95% Stable up to 6 months at 4 °C Increased inhibition of UKF-NB3 and IMR-32 cell lines, compared with free doxorubicin	[43]
BSA	–	Ginsenoside CK	Lung, skin, colon cancer, and hepatocarcinoma (A549, HaCaT, HT29, and HepG2 cell lines)	Particle diameter: 30–50 nm, ZP: −70.8 mV. Nanoparticles were stable at biological pH and were readily degraded in acidic conditions, enhanced water solubility of ginsenoside CK. Increased antiproliferative activity toward HT29, A546, HepG2, and HaCaT cancer cell lines.	[44]
BSA	–	Salicylic acid (SA)	–	Particle diameter: 110 nm, ZP: −33.2 mV, DEE: 55% at pH 7.4 Increases the bioavailability of SA Instant release, progressive up to 120 min, then constant release of SA up to 400 min	[33]
BSA	Folic acid	Tamoxifen (TMX)	Breast cancer	Particle diameter: 76–417 nm, ZP: −10 to −43 mV Folic acid: for selective delivery of TMX Rapid in the first 2 h, followed by sustained release of TMX up to 24 h. Enhanced release in acidic conditions • Enhanced cellular uptake and effective in reducing carcinoma cell survival	[46]
BSA	Folic acid	Bexarotene (BXT)	Breast cancer (MCF-7 cell line)	Particle diameter: 195.3 nm, ZP: −33.64 mV, DEE: 65%, DLC: 1.7% Folate receptors are overexpressed in MCF-7 Initial burst release (39% in 12 h), followed by up to 69% of slow release of BXT in 48 h, then sustained release up to 72 h • Greater antiproliferative effect on MCF-7 cells	[47]
HSA	Folic acid and magnetic nanoparticles	Cisplatin	–	Particle diameter: 9 nm, DLC: 5.3%, DEE: 90% Folate receptors are overexpressed in cancer cells • Sustained release of cisplatin for 24 h without burst release • The nanocarrier has selective chemotherapy action, along with thermotherapy	[48]
BSA	Folic acid	Chrysin (CHA)	Breast cancer (MCF-7 cell line)	Particle diameter: 97.5 nm, ZP: −11.0 mV Folate receptors are overexpressed in cancer cells • Initial burst (20%) in 10 h, followed by cumulative 57% sustained release of CHA up to 96 h • Enhanced cellular uptake and cytotoxicity toward MCF-7 cell line	[49]
HSA	PEI	Gallic acid (GA)	Parkinson disease (PC-12 neuroendocrine cell line)	Particle diameter: 117 nm and 180 nm, ZP: +35.2 mV and +34.2 mV, respectively • DLC and DEE depend on GA-to-PEI-HSA ratio, Initial burst (30%) in 1.5 h, followed by sustained release of GA up to 48 h. No significant toxicity toward PC-12 cells	[50]
HSA	PEI	Doxorubicin	Breast cancer (MCF-7 cell line)	Particle diameter: 137 nm, ZP: +15 mV 80% of cells were transfected due to positive surface charge • Exhibited greater cytotoxic effect against MCF-7 cancer cell lines	[51]
HSA	PEG	Tamoxifen (TMX)	Tumor target	Particle diameter: 195 nm, ZP: −21 mV, DEE: 74%, DLC: 7% Only a slight increase in particle size after 3 months of storage • Ultrasonication of TMX-HSA mixture was done before desolvation	[52]
BSA	Lactobionic acid	Oridonin (ORI)	Liver cancer	Particle diameter: 200 nm, ZP: −30 mV, DLC: 5%, DEE: 63% Galactosylated BSA: for selective liver targeting • Initial burst, followed by sustained release of ORI up to 70 h.	[53]
BSA	Galactosamine	Doxorubicin (DOX)	Hepatocarcinoma (HepG2 cell line)	Particle diameter: 200 nm, ZP: −16.1 mV, DEE: 58%, DLC: 2% Asialoglycoprotein receptors are overexpressed in HepG2 cells • Slow release (5% in 5 h), followed by 12% sustained release of DOX up to 160 h • Increased cellular uptake causes more cytotoxicity toward HepG2 cells.	[54]
HSA	–	Paclitaxel and gold nanorods	Breast cancer (4T1 cell line in mouse)	Particle diameter: 221 nm, ZP: −45 mV, DEE: 92% combined (chemo + photothermal) therapy • 94% of 4T1 cell death on 15-min exposure to near-infrared light	[57]
BSA	Polycaprolactone (PCL)	Albendazole (ABZ)	Pancreatic cancer	Particle diameter: 10 and 200 nm, DEE: 68% (10 nm) and 81% (100 nm) BSA-PCL nanoparticles of 200 nm effectively deliver ABZ to pancreatic cells and show a greater antiproliferative effect on cancer cells	[58]
HSA	SP and PEG	Paclitaxel (PTX)	Brain cancer	Particle diameter: 150 nm, ZP: −12.0 mV, DLC: 8%, DEE: 86% Substance P (SP) receptors are overexpressed in glioma sites • Initial burst (40%), followed by the sustained release of PTX up to 48 h • The targeting effect of SP increases the cellular uptake and nanoparticles exhibit strong antitumor effect toward U87 cells	[59]
BSA	Magnetic nanoparticles	–	–	Particle diameter: 70–95 nm, ZP: −9.38 mV Biocompatible and do not show a toxic effect on HFF2 cell lines • Can be used in MRI technique and chemothermotherapy	[60]
BSA	Magnetic nanoparticles	Curcumin (CUR)	Breast cancer (MCF-7 cell line)	Particle diameter: 56 nm, ZP: −10.1 mV, DLC: 7% Initial burst, followed by sustained release of CUR up to 160 h. Enhanced release in acidic conditions • Biocompatible and showed a significant cytotoxic effect on MCF-7 cells	[61]
BSA	–	Curcumin (CUR)	Breast cancer (MDA-MB-231 cell line)	Particle diameter: 223.5 nm, ZP: −31.7 mV, at drug polymer ratio of 1:2, DEE: 91%. Enhancement in the solubility of CUR Initial burst (23%) in 24 h, followed by the sustained release of CUR up to 30 days • Enhanced antiproliferative effect toward MDA-MB-231	[62]
Egg albumin	–	Gallic acid (GA)	Brain cancer	Particle diameter: 150 nm, ZP: −30 mV, DLC: 28%, DEE: 91% A good candidate for brain-targeted drug delivery system	[63]
BSA	–	Sulfasalazine (SSZ)	–	Particle diameter: 208–381 nm, ZP: −24.6 to −36.3 mV, DLC: 0.5%, DEE: 28% Enhanced solubility of SSZ	[64]
BSA	–	Curcumin (CUR)	Breast cancer (MCF-7 cell line)	Particle diameter: 92.6 nm, ZP: −9.2 mV, DLC: 2.2%, DEE: 78% Rapid in 10 h (20%), followed by controlled release of 30% of CUR up to 96 h • Cytotoxic toward MCF-7, inhibitory effect increases with time	[65]
HSA	–	Doxorubicin (DXR), daunorubicin (DNR), pirarubicin (THP), and aclarubicin (ACR)	Breast cancer (MCF-7 cell line)	DXR-HSA-NPs: particle diameter: 108 nm, ZP: −35 mV, DLC: 4%, DEE: 96% DNR-HSA-NPs: particle diameter: 109 nm, ZP: −33 mV, DLC: 6%, DEE: 97% THP-HSA-NPs: particle diameter: 121 nm, ZP: −43 mV, DLC: 2.6%, DEE: 88% ACR-HSA-NPs: particle diameter: 119 nm, ZP: −45 mV, DLC: 1%, DEE: 30% All anthracycline-HSA-NPs exhibit cytotoxicity toward MCF-7 and HepG2 cells	[66]
HSA	–	Pyrazolo[3,4-d] pyrimidine	Neuroblastoma (SH-SY5Y cell line)	Particle diameter: 50–115 nm, ZP: −29.9 mV, DEE: 40%–99.5%., DLC: 39%–95% Improved drug solubility • Enhanced antiproliferative effect on SH-SY5Y.	[67]
BSA	Folic acid	Curcumin difluorinated (CDF)	Ovarian cancer (SKOV 3 cell line)	Particle diameter: 279 nm, ZP: −45.9 mV, DEE: 78%, DLC: 38% Higher cellular uptake causes enhanced cytotoxicity	[68]

^†All particle diameters are approximate; BSA, bovine serum albumin; DEE, drug entrapment efficiency (approximate); DLC, drug-loading capacity (approximate); Egg albumin = ovalbumin; HSA, human serum albumin; MRI, magnetic resonance imaging; PEG, polyethylene glycol; PEI, polyethylenimine; RSM, response surface methodology; ZP, zeta potential.