# Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals

**Authors:** Alam Zeb, Isra Rana, Ho-Ik Choi, Cheol-Ho Lee, Seong-Woong Baek, Chang-Wan Lim, Namrah Khan, Sadia Tabassam Arif, Najam us Sahar, Arooj Mohsin Alvi, Fawad Ali Shah, Fakhar ud Din, Ok-Nam Bae, Jeong-Sook Park, Jin-Ki Kim

PMC · DOI: 10.3390/pharmaceutics12121184 · Pharmaceutics · 2020-12-06

## TL;DR

Nanocarriers can improve the delivery of biopharmaceuticals, making them more effective and less harmful.

## Contribution

This review highlights the potential of nanocarriers for efficient delivery of various biopharmaceuticals through multiple routes.

## Key findings

- Nanocarriers protect biopharmaceuticals from degradation and enhance their delivery.
- They enable noninvasive delivery routes like oral, pulmonary, nasal, and skin.
- Combining nanocarriers with biopharmaceuticals can improve future healthcare products.

## Abstract

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Trf (transferrin) [NCBI Gene 22041] {aka Cd176, HP, Tf, Tfn, hpx}, Ms4a1 (membrane-spanning 4-domains, subfamily A, member 1) [NCBI Gene 12482] {aka Cd20, Ly-44, Ms4a2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Ar (androgen receptor) [NCBI Gene 24208] {aka Andr, Tfm}, SLC3A2 (solute carrier family 3 member 2) [NCBI Gene 6520] {aka 4F2, 4F2HC, 4T2HC, CD98, CD98HC, MDU1}, Gja1 (gap junction protein, alpha 1) [NCBI Gene 14609] {aka Cnx43, Cx43, Cx43alpha1, Cxnk1, Gja-1, Npm1}, GPRC6A (G protein-coupled receptor class C group 6 member A) [NCBI Gene 222545] {aka GPCR, bA86F4.3}, Erbb2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 13866] {aka Erbb-2, HER-2, HER2, Neu, c-erbB2, c-neu}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, Pth (parathyroid hormone) [NCBI Gene 19226] {aka Pthp}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, Plat (plasminogen activator, tissue type) [NCBI Gene 25692] {aka PATISS, tPA}, Prom1 (prominin 1) [NCBI Gene 19126] {aka 4932416E19Rik, AC133, CD133, Prom, Prom-1, Proml1}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, CLEC3B (C-type lectin domain family 3 member B) [NCBI Gene 7123] {aka MCDR4, TN, TNA}, Calca (calcitonin/calcitonin-related polypeptide, alpha) [NCBI Gene 12310] {aka CA, CGRP-1, CGRP1, Calc, Calc1, Cgrp}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, EIF5B (eukaryotic translation initiation factor 5B) [NCBI Gene 9669] {aka IF2}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, Csf3 (colony stimulating factor 3) [NCBI Gene 25610] {aka Gcsf}, CCR4 (C-C motif chemokine receptor 4) [NCBI Gene 1233] {aka CC-CKR-4, CD194, CKR4, CMKBR4, ChemR13, HGCN:14099}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, Sost (sclerostin) [NCBI Gene 74499] {aka 5430411E23Rik}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, Hgf (hepatocyte growth factor) [NCBI Gene 24446] {aka HPTA}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}
- **Diseases:** Thrombosis (MESH:D013927), liver failure (MESH:D017093), triple-negative breast cancer (MESH:D064726), hereditary transthyretin-mediated amyloidosis (MESH:C567782), Hypovolemia (MESH:D020896), hepatic steatosis (MESH:D005234), Duchenne muscular dystrophy (MESH:D020388), Autoimmune disorders (MESH:D001327), diseases (MESH:D004194), Neutropenia (MESH:D009503), glioblastoma (MESH:D005909), Osteoporosis (MESH:D010024), nephritis (MESH:D009393), ascites (MESH:D001201), Peptic ulcer (MESH:D010437), deficiency in beta-galactosidase (MESH:D016537), ankylosing spondylitis (MESH:D013167), acquired immunodeficiency syndrome (MESH:D000163), hypoglycemic shock (MESH:C000721848), infection (MESH:D007239), beta thalassemia (MESH:D017086), metastasis (MESH:D009362), infectious and inflammatory diseases (MESH:D003141), inflammatory bowel disease (MESH:D015212), bleeding (MESH:D006470), Blastic plasmacytoid dendritic cell neoplasm (MESH:D018307), Dengue (MESH:D003715), colonic inflammation (MESH:D007249), ischemic (MESH:D002545), lymphoma (MESH:D008223), Fabry disease (MESH:D000795), tetanus (MESH:D013746), X-linked disorder (MESH:D040181), ulcerative colitis (MESH:D003093), Non-Hodgkin lymphoma (MESH:D008228), Type 2 diabetes (MESH:D003924), ischemic tissues (MESH:D017695), Leishmania major infection (MESH:D007896), Crohn's disease (MESH:D003424), brain tumors (MESH:D001932), Gaucher's disease (MESH:D005776), Thyroid eye disease (MESH:D049970), psoriatic arthritis (MESH:D015535), intracranial gliomas (MESH:D005910), Leukemia (MESH:D007938), bone resorption (MESH:D001862), Ovarian cancer (MESH:D010051), hepatitis B (MESH:D006509), Hormone Hormone deficiency (MESH:D004393), Myocardial infarction (MESH:D009203), Primary humoral immunodeficiency (MESH:C562390), Immune cells Ab Immune thrombocytopenic purpura (MESH:D016553), hematological problems (MESH:D006402), Deep vein thrombosis (MESH:D020246), Nonalcoholic fatty liver disease (MESH:D065626), immune diseases (MESH:D007154), HIV (MESH:D015658), Spinal muscular atrophy (MESH:D009134), juvenile idiopathic arthritis (MESH:D001171), Thromboembolic diseases (MESH:D013923)
- **Chemicals:** Emapalumab (MESH:C000644327), suberoylanilide hydroxamic acid (MESH:D000077337), glycol (MESH:D006018), Chitosan (MESH:D048271), Dextran (MESH:D003911), Magnetite (MESH:D052203), calcium (MESH:D002118), HP55 (MESH:C053309), G3139 (MESH:C408162), alginate (MESH:D000464), oil (MESH:D009821), cholesterol (MESH:D002784), Docetaxel (MESH:D000077143), polyester urethane (MESH:C081821), MTT (MESH:C070243), sucrose (MESH:D013395), diamine (MESH:D003959), Tween 80 (MESH:D011136), Salinomycin (MESH:C010327), Rituximab (MESH:D000069283), thiol (MESH:D013438), Nutlin-3 (MESH:C482205), hyaluronic acid (MESH:D006820), 1,2-dioleoyl-3-trimethylammonium-propane (MESH:C070046), Methotrexate (MESH:D008727), Lipid (MESH:D008055), Melatonin (MESH:D008550), PS (MESH:D010758), Au (MESH:D006046), PLGA (MESH:D000077182), blood glucose (MESH:D001786), PLA (MESH:C033616), Teprotumumab (MESH:C551399), PVA (MESH:D011142), FA (MESH:D005492), fatty acids (MESH:D005227), paclitaxel (MESH:D017239), polymers (MESH:D011108), phospholipids (MESH:D010743), PEG (MESH:D011092), doxorubicin (MESH:D004317), Cisplatin (MESH:D002945), Eudragit  RS (MESH:C050528), Oligonucleotide (MESH:D009841), silica (MESH:D012822), Adalimumab (MESH:D000068879), Glycosaminoglycan (MESH:D006025), thioglycolic acid (MESH:C017487), glucose (MESH:D005947), sorbitan oleate (MESH:C018665), ZP (MESH:C017803), Doxil (MESH:C506643), tricaprin (MESH:C010800), Pertuzumab (MESH:C485206), muromonab (MESH:D016853), glycerides (MESH:D005989), Bortezomib (MESH:D000069286), disulfide (MESH:D004220), Calcium phosphate (MESH:C020243), Ravulizumab (MESH:C000629409)
- **Species:** Human papillomavirus (species) [taxon 10566], Ebola virus [taxon 186536], Hepatitis B virus (no rank) [taxon 10407], Enterovirus C (no rank) [taxon 138950], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090], Human immunodeficiency virus (species) [taxon 12721], Rattus norvegicus (brown rat, species) [taxon 10116], Leishmania (subgenus) [taxon 38568], Bacillus anthracis (anthrax bacterium, species) [taxon 1392], Tequatrovirus T4 (species) [taxon 10665], Helicobacter pylori (species) [taxon 210], Yersinia pestis (species) [taxon 632], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** insect — Trichoplusia ni (Cabbage looper), Spontaneously immortalized cell line (CVCL_C190), Mrc-5 — Mus musculus (Mouse), Transformed cell line (CVCL_5U93), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), A431 — Homo sapiens (Human), Skin squamous cell carcinoma, Cancer cell line (CVCL_0037), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), Nb2-11 — Rattus norvegicus (Rat), Rat malignant lymphoma, Cancer cell line (CVCL_3860), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), BT474 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0179)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7762162/full.md

## References

182 references — full list in the complete paper: https://tomesphere.com/paper/PMC7762162/full.md

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Source: https://tomesphere.com/paper/PMC7762162