Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature

Figures & data

Figure 1 The main biomedical application of polymeric nanocapsules/nanocarriers.

Notes: PubMed resources searched in all fields using the term “polymeric nanocapsules” filtered on “in the last five years” (2016–2020). Seven hundred seventy results were obtained (on March 25, 2020), and the authors selected 320 publications in which nanocapsules were used in the biomedical field (excluding diagnostic application and review papers). (A) Polymer nanocapsules were divided into three categories depending on their application in medicine. (B) Since the vast majority were nanocapsules used as a drug delivery system (294 from 320 publications), the authors present the types of transported drugs, w/o drugs stand for nanocapsules which were obtained empty and have potential as drug transporter.

Figure 2 Schematic illustration of nanocarriers (A) nanocapsules (B) nanoparticle/nanospheres.

Figure 3 Schematic representation of selected polymeric nanocarriers.

Figure 4 Schematic illustration of the layer by layer method.

Figure 5 Schematic illustration of the nanoprecipitation method. Nanocarriers are formed by polymer precipitation caused by organic solvent removal by evaporation or diffusion. Data from Weiss et al¹¹ and Keech et al¹³.

Figure 6 Schematic illustration of the nanoemulsion templated methods. Nanocarriers are formed by polymer precipitation, interfacial phenomena, or coacervation caused by organic solvent removal by evaporation or diffusion. ^{11 13}Data from Weiss et al¹¹ and Keech et al¹³.

Figure 7 Schematic representation of water in oil in water (w/o/w) and oil in water in oil o/w/o emulsions.

Table 1 Polymeric Nanocapsules Obtained and Characterized in vivo for Delivery of Various Anticancer Compounds

Nanocarriers	Drug	Route of Administration	Animal Model	Targeting
PCL nanocarriers^Citation127	2-(2-Methoxyphenyl)-3-((Piperidin-1-yl)ethyl)thiazolidin-4-one	Orally	Healthy Wistar rats	Passive
PCL nanocarriers^Citation128	Diphenyl diselenide	i.g.	Wistar rats, healthy or tumor-bearing rats after injection of C6 (rat glioma) cells in the right striatum	Passive
Polyurethane nanocarriers^Citation129	Doxorubicin	-	Zebrafish	Active – mitochondria
PEGylated polypyrrole nanocarriers^Citation79	Doxorubicin	i.v.	Tumor-bearing athymic nude mice after subcutaneous injection of Skov3 (human ovarian carcinoma) cells	Active – folate receptor
Spherical SiO2 structured PDADMAC, PAZO NaGdF4, Yb, Tm@NaYF4@NaGdF4, Nd@NaYF^Citation130	Doxorubicin	i.v.	Tumor-bearing BALB/c nude mice after subcutaneous injection of U87-MG (human glioblastoma) cells	Light-triggered drug delivery
Poly-L-arginine nanocarriers^Citation131	Elisidepsin	Orally	Healthy mice	Passive
PEGylated b-poly(L-aspartic acid) nanocarriers^Citation132	Erlotinib	i.v.	Tumor-bearing BALB/c nude mice after subcutaneous injection of HCC-827 (human lung adenocarcinoma) cells	Passive
PEGylated lipid based nanosuspention^Citation133	Etoposide	i.v.	Healthy Kunming mice and tumor-bearing BALB/c mice after subcutaneous injection of A20 (murine lymphoma) cells	Passive
PCLlipid core nanocarriers^Citation134	Eugenol or acetyl eugenol	Orally or i.p.	Tumor-bearing C57Bl6 mice after subcutaneous injection of B16F10 (murine melanoma) cells	Passive
PEGylated lipid squalene nanocarriers^Citation135	Gemcitabine	Convection-enhanced delivery (the infusion of therapeutic molecules directly into the brain)	Healthy Sprague- Dawley or tumor-bearing Fischer 344 rats after intracranial implantation of RG2 (rat glioma) cells	Passive
PEGylated PLGA nanocarriers^Citation136	Glabrescione b	i.v.	Tumor-bearing SCID/Beige mice after subcutaneous injection of PANC-1 (human pancreas carcinoma) cells	Passive
PCLnanocarriers^Citation137	Methotrexate	Orally or i.v.	Healthy or tumor-bearing C57Bl/6 mice after intracranial implantation of GL261 (murine glioma) cells	Passive
Chitosan and Eudragit S100 nanocarriers^Citation138	Psoralidin	Orally	Healthy Sprague-Dawley rats	Passive
PCL nanocarriers^Citation139	Resveratrol	i.p.	Tumor-bearing C57BL/6J mice after subcutaneous injection of B16F10 (murine melanoma) cells	Passive
PLA nanocarriers^Citation140	Tamoxifen	i.v.	Tumor-bearing Swiss albino mice after subcutaneous injection of MCF-7 (human breast cancer estrogen receptor-positive) cells	Passive
Polydopamine nanocarriers^Citation141	Zeolitic nanocrystals	i.p.	Healthy Sprague- Dawley rats	Passive

Abbreviations: i.g., intragastric; i.p., intraperitoneal; i.v., intravenous; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol); PLA, poly(lactide).

Table 2 Polymeric Nanocarriers Obtained and Characterized in vivo for Delivery of More Than One Chemotherapeutic

Nanocarriers	Drug	Route of Administration	Animal Model	Targeting
PLGA nanocarriers^Citation142	Doxorubicin; berberine	i.v.	Healthy Sprague- Dawley rats	–
Poly(methyl vinyl ether-co-maleic anhydride) nanocarriers^Citation143	Doxorubicin; selol	i.v.	Tumor-bearing BALB/c mice after subcutaneous injection of 4T1 (mouse mammary carcinoma) cells	–
PLGA nanocarriers^Citation144	Oxaliplatin, irinotecan, and 5-fluorouracil	i.v.	Tumor-bearing BALB/c (nu/nu) nude mice after subcutaneous injection of SW1990 or Panc-1 (human pancreatic cancer) cells	–
PEGylated lipid bilayer coated mesoporous silica nanocarriers^Citation145	Paclitaxel; curcumin	i.v.	Tumor-bearing BALB/c nude mice after subcutaneous injection of CIPp (canine breast cancer) cells	–
PLGA nanocarriers^Citation146,Citation147	Paclitaxel; perfluorooctyl bromide	i.v.	Tumor-bearing Fox1nu (nu/nu) mice after subcutaneous injection of CT-26 (murine colon cancer) cells	–

Abbreviations: i.v., intravenous; PEG, poly(ethylene glycol); PLGA, poly(lactide-co-glycolide).

Table 3 Polymeric Nanocarriers Obtained and Characterized in vivo for Delivery of Different Drugs for Lifestyle Disease

Nanocarriers	Transporting Agent	Route of Administration	Animal Model	Application	Targeting
PEGylated nanocarriers^Citation148	Rivaroxaban	Orally or i.v.	Healthy or blood vessel inflammation-induced albino rats	Venous thromboembolism treatment	–
Chitosan and gum arabic polymeric nanocarriers and polysorbate-80 nanocarriers^Citation149	Glycyrrhizin and thymoquinone	Orally	Streptozotocin and nicotinamide–induced diabetic Wistar albino rats	Diabetes mellitus treatment	–
Eudragit RSPO-Lutrol F 127 nanocarriers^Citation150	Felodipine	Orally	Healthy Sprague- Dawley rats	Hypertension treatment	–
PLGA nanocarriers^Citation151	Curcumin capped gold nanoparticles	s.c.	Enalapril-induced cardiac hypertrophy Wister rats	Cardiac hypertrophy reduction	–
PCL-PEG nanocarriers^Citation152	Cilostazol	Orally	Healthy Wistar rats	Peripheral arterial disease treatment	–
Eudragit S 100 nanocarriers^Citation153	Budesonide	Orally	Colitis-induced Wister albino rats	Inflammatory bowel disease treatment	pH-sensitive

Abbreviations: i.v., intravenous; s.c., subcutaneous; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol); PLGA, poly(lactide-co-glycolide).

Table 4 Polymeric Nanocarriers Obtained and Characterized in vivo for Delivery of Anti-Inflammatory Drugs

Nanocarriers	Drug	Route of Administration	Animal Model	Targeting
Hyaluronic acid niosomes^Citation154	Curcumin	Orally	Rats with carrageenan-induced paw edema	–
Starch-based nanocarriers^Citation155	Neutrophil elastase inhibitor (ER143)	Topical	The croton oil-induced ear inflammation in BALB/c mice	–
PCL nanocarriers^Citation156	Nerolidol	i.p.	Zymosan-induced arthritis in Swiss mice	–
PCL nanocarriers^Citation157	Resveratrol	Orally	Challenged with LPS A/J mice	–
PEGylated nanocarriers^Citation158	Meloxicam	Orally	Healthy C57BL/6 mice	–

Abbreviations: i.p., intraperitoneal; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol).

Table 5 Polymeric Nanocarriers Obtained and Characterized in vivo for Delivery of Drugs for Neurological Disorders

Nanocarriers	Transporting Agent	Route of Administration	Animal Model	Application	Targeting
PCL nanocarriers^Citation159	p,p’-methoxyl-diphenyl diselenide	i.g.	Swiss mice with the chronic pain-like behavior induced by the partial sciatic nerve ligation surgery	Neuropathic pain treatment	–
Polysorbate 80; chitosan PEGylated nanocarriers^Citation160	Clozapine	i.p. or i.v.	Healthy or amphetamine-induced pseudo-psychosis Wistar rats	Schizophrenia treatment	–
NFL-TBS.40–63 polypeptide nanocarriers^Citation161	–	Injection in the brain right lateral ventricle or the spinal cord	Healthy Sprague- Dawley rats	Neuronal disorders treatment	Neural stem cells
PLGA nanocarriers containing triphenylphosphonium^Citation162	Quercetin	Oral gavage	Cerebral ischemia-induced in Wistar rats	Neuro-protective role in cerebral ischemia-reperfusion	Mitochondria
Lecithin/chitosan nanocarriers^Citation163	Simvastatin	Intranasally	Healthy Wistar rats	Neuro-degenerative diseases treatment	–

Abbreviations: i.g., intragastric; i.p., intraperitoneal; i.v., intravenous; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol); PLGA, poly(lactide-co-glycolide).

Table 6 Polymeric Nanocarriers Obtained and Characterized in vivo for Delivery of Drugs Against Infectious Diseases

Nanocarriers	Transporting Agent	Route of Administration	Animal Model	Application	Targeting
Eudragit L-100 nanocarriers^Citation164	Curcumin	Orally	Healthy or Listeria monocytogenes-infected gerbils	Bacterial infection treatment	pH-sensitive
Cellulose acetate phthalate nanocarriers^Citation165	Eugenol; Chlorhexidine	Orally	Healthy volunteers with periodontal disease	Bacterial infection treatment (periodontal disease)	pH-sensitive
PCL nanocarriers^Citation166	Itraconazole	Topical application in the vagina	BALB/c mice inoculated intravaginally with Candida albicans	Fungal infection treatment (vulvovaginal candidiasis)	–
PLGA-PEG nanocarriers^Citation167–Citation170	Lychnopholide	Orally or i.v.	Healthy or Trypanosoma cruzi- infected Swiss mice; healthy C57BL/6 mice	Parasite infection treatment (Chagas disease)	–
PCL nanocarriers^Citation171	Quercetin; penta-acetylated derivative of quercetin	Intragastric gavage	Leishmania amazonensis-infected BALB/c mice	Parasite infection treatment (Leishmaniasis)	–
Eudragit^® RS100 or polysorbate 80 nanocarriers^Citation172	Quinine	i.v.	Plasmodium berghei-infected Wistar rats	Parasite infection treatment (malaria)	–
Heparin nanocarriers^Citation173	Artesunate	i.v.	Healthy BALB/c mice	Parasite infection treatment (malaria)	–
Polysorbate 80 nanocarriers or Eudragit^® RS100 nanocarriers^Citation174,Citation175	Quinine; curcumin	i.p.	Wild-type N2 Bristol strain of Caenorhabditis elegans; Plasmodium berghei-infected Swiss mice	Parasite infection treatment (malaria)	–
PCL nanocarriers^Citation176	Artemether	Orally	Healthy and Plasmodium berghei-infected C57BL/6 mice	Parasite infection treatment (malaria)	–

Abbreviations: i.g., intragastric; i.p., intraperitoneal; i.v., intravenous; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol); PLGA, poly(lactide-co-glycolide).

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