Table 1:
Marketed NDDS (Anselmo & Mitragotri, 2019; Bulbake et al., 2017; Farjadian et al., 2019; FDA, 2020a, 2020b; Wang et al., 2013; Weissig et al., 2014)
| PRODUCT | API | ROUTE | INITIAL APPROVAL |
INDICATION | COMPANY |
|---|---|---|---|---|---|
| LIPOSOME | |||||
| Doxil® | Doxorubicin Hydrochloride |
i.v. | FDA, 1995 | Ovarian, breast cancer, multiple myeloma, Kaposi’s sarcoma | Baxter Healthcare Corp |
| Curosurf® | Poractant alfa | intratracheal injection | FDA 1999 | Respiratory Distress Syndrome (RDS) | Chiesi USA Inc |
| Myocet liposomal® | Doxorubicin (Non-pegylated) | i.v. | Europe, 2000 | Breast neoplasm | Teva B. V. |
| Mepact® | Mifamurtide | i.v. | Europe, 2009 | Osteosarcoma | Takeda France SAS |
| Marqibo® | Vincristine Sulfate | i.v. | FDA, 2012 | Philadelphia chromosome -negative acute lymphoblastic leukemia | Acrotech |
| Onivyde® | Irinotecan Hydrochloride | i.v. | FDA, 1996 | Combination therapy with fluorouracil and leucovorin in metastatic adenocarcinoma of pancreas | Ipsen Inc |
| AmBisome® | Amphotericin -B | i.v. | FDA, 1997 | Systemic fungal infections | Astellas, Gilead |
| Exparel® | Bupivacaine | i.v. | FDA, 1972 | Postsurgical analgesia | Pacira Pharms Inc |
| Caelyx® | Doxorubicin Hydrochloride | i.v. | Europe, 1996 | Kaposi’s sarcoma, multiple myeloma, ovarian & breast neoplasm | Janssen Cilag International NV |
| Vyxeos™ | Cytarabine and Daunorubicin | i.v. | FDA, 2017 | Therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) | Celator Pharms |
| DaunoXome® | Daunorubicin Citrate | i.v. | FDA 1996 (Discontinued) | Advanced HIV-associated Kaposi's sarcoma | Galen (UK) |
| DepoCyt® | Cytarabine | Intrathecal injection | FDA 1999 (Discontinued) | Lymphomatous meningitis | Pacira Pharms Inc |
| DepoDur® | Morphine sulfate | Epidural injection | FDA 2004 (Discontinued) | Pain following major surgery | Pacira Pharms Inc |
| Epaxal® | Hepatitis A virus (inactivated) | i.m. | Europe 2000 (Discontinued) | Hepatitis A vaccine | Berna Biotech Ltd |
| LIPID-BASED NANOPHARMACEUTICALS | |||||
| Abelcet® | Amphotericin B lipid complex | i.v. | FDA, 1995 | Invasive severe fungal infections | Leadiant Biosci Inc |
| Onpattro® | Patisiran (small interfering RNA) | i.v. | FDA 2018 | Polyneuropathy of hereditary transthyretin-mediated amyloidosis | Alnylam Pharms Inc |
| Pfizer-BioNTech COVID-19 Vaccine | messenger ribonucleic acid (mRNA) | i.m. | FDA 2020 | Prevention of 2019 coronavirus disease (COVID-19) for individuals 12 years of age and older | Pfizer Inc. |
| Moderna COVID-19 Vaccine | messenger ribonucleic acid (mRNA) | i.m. | FDA 2020 | Prevention of 2019 coronavirus disease (COVID-19) for individuals 18 years of age and older | ModernaTX, Inc. |
| PEGYLATED PROTEIN, POLYPEPTIDES, APTAMERS | |||||
| Cimzia® | Certolizumab pegol (Pegylated Fab’ fragment of humanized anti-tumor necrosis factor -alpha antibody) | s.c. | FDA, 2008 | Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis | UCB Inc |
| Neulasta® | Pegylated Filgrastim | s.c. | FDA, 2002 | Febrile neutropenia, hematopoietic subsyndrome of acute radiation syndrome | Amgen |
| Neupogen® | Filgrastim | s.c., i.v. | FDA 1991 | Febrile neutropenia, hematopoietic subsyndrome of acute radiation syndrome | Amgen |
| Nivestym | Filgrastim-aafi | s.c., i.v. | FDA 2018 | Febrile neutropenia, hematopoietic subsyndrome of acute radiation syndrome | Hospira Inc |
| Granix® | Tbo-filgrastim | s.c. | FDA 2012 | neutropenia in patients with non-myeloid malignancies | Sicor Biotech |
| Nyvepria™ | Pegfilgrastim-apgf | s.c. | FDA 2020 | Febrile neutropenia | Hospira Inc |
| Udenyca® | Pegfilgrastim-cbqv | s.c. | FDA 2018 | Febrile neutropenia | Coherus Biosciences Inc |
| Zarxio® | Filgrastim-sndz | s.c. | FDA 2015 | Febrile neutropenia | Sandoz Inc |
| Ziextenzo™ | Pegfilgrastim-bmez | s.c. | FDA 2019 | Febrile neutropenia | Sandoz Inc |
| Fulphila® | Pegfilgrastim-jmdb | s.c. | FDA 2018 | Febrile neutropenia | Mylan Gmbh |
| Oncaspar® | Pegaspargase | i.m., i.v. | FDA, 1994 | Acute lymphoblastic leukemia | Sigma Tau |
| Pegasys® | Pegylated Interferon alfa-2a | s.c. | FDA, 2002 | Hepatitis B and C | Hoffman-LA Roche |
| Somavert® | Pegvisomant | s.c. | FDA, 2003 | Acromegaly | Pharmacia |
| Mircera® | Methoxy polyethylene glycol-epoetin beta | i.v., s.c. | FDA, 2007 | Anemia associated with chronic kidney disease (CKD) | Hoffman-LA Roche |
| PegIntron® | Pegylated Interferon alfa-2b | s.c. | FDA, 2001 | Hepatitis C | Schering |
| Krystexxa® | Pegloticase (Pegylated uric acid specific enzyme) | i.v. | FDA, 2010 | Chronic gout | Horizon Pharma |
| Plegridy® | PEG-IFN-ß-1a | s.c. | FDA, 2014 | Multiple sclerosis (relapsing forms) | Biogen Idec Inc |
| Sylatron™ | Peginterferon alfa-2b | s.c. | FDA 2011 | melanoma with microscopic or gross nodal involvement | Schering |
| Adynovate® | Pegylated anti-hemophilic factor (Recombinant) | i.v. | FDA, 2015 | Hemophilia A (congenital factor VIII deficiency) | Baxalta US Inc. |
| Rebinyn® | Coagulation Factor IX (Recombinant), GlycoPEGylated | i.v. | FDA, 2017 | Hemophilia B | Novo Nordisk Inc. |
| Adagen® | Pegademase bovine enzyme | i.v. | FDA 1990 (Discontinued) | Severe combined immunodeficiency disease (SCID) associated with a deficiency of ADA | Leadiant Biosci Inc |
| Macugen® | Pegaptanib sodium | intravitreal injection | FDA 2004 (Discontinued) | Neovascular (wet) age-related macular degeneration | Valeant Pharms LLC |
| PROTEIN-DRUG CONJUGATES | |||||
| Abraxane® | Paclitaxel protein-bound particles (albumin-bound) | i.v. | FDA, 2005 | Metastatic breast cancer, locally advanced or metastatic non-small cell lung cancer (NSCLC), Metastatic adenocarcinoma | Abraxis Bioscience LLC |
| Ontak® | Denileukin diftitox (Recombinant fusion protein of fragment A of diphtheria toxin and interleukin-2) | i.v. | FDA, 1999 | Persistent or recurrent cutaneous T-cell lymphoma | Eisai Inc |
| Kadcyla® ado-trastuzumab emtansine) | Ado-trastuzumab emtansine (Antibody-drug conjugate) | i.v. | FDA, 2013 | HER2-positive, metastatic breast cancer (MBC), Early Breast Cancer (EBC) | Genentech |
| Taxol® | Paclitaxel | i.v. | FDA 1992 (Discontinued) | Advanced carcinoma of the ovary | HQ Spclt Pharma |
| OTHER TYPES OF POLYMER-BASED NANOPHARMACEUTICALS | |||||
| Copaxone® | Glatiramer acetate | s.c. | FDA, 1996 | Multiple sclerosis (relapsing forms) | Teva Pharms USA |
| Eligard®Kit | Leuprolide acetate incorporated in PLGH (DL-lactide / glycolide; 1/1, molar) NPs | s.c. | FDA, 2002 | Advanced prostate cancer (palliative treatment) | Tolmar Therap |
| Renagel® | Sevelamer Hydrochloride | oral | FDA, 2000 | Hyperphosphatemia (in chronic kidney disease) | Genzyme |
| Alimta® | Pemetrexed | i.v. | FDA 2004 | Advanced or metastatic, non-squamous, non-small cell lung cancer (NSCLC), Platinum chemotherapy, | Lilly |
| Genexol® | Paclitaxel micelles of poly(ethylene glycol)-poly (D,L-lactide) | i.v. | South Korea, 2001 | Metastatic breast cancer, pancreatic cancer | Samyang Biopharmaceuticals Corporation (Seoul, Korea) |
| Zinostatin stimalamer® | Neocarzinostatin (Conjugate protein or copolymer of styrene-maleic acid and an antitumor protein NCS) | Intrahepatic injection | Japan, 1994 | Primary unresectable hepatocellular carcinomas | Yamanouchi |
| Zilretta® | Triamcinolone acetonide | intra-articular injection | FDA 1957 | osteoarthritis pain of the knee | Flexion Therapeutics Inc |
| NANOCRYSTALS | |||||
| Emend® | Aprepitant | oral | FDA, 2003 | Antiemetic | Merck |
| Emend® | Fosaprepitant Dimeglumine (prodrug) | i.v. | FDA 2008 | Antiemetic | Merck and Co Inc |
| Ostim® | Calcium Hydroxyapatite | paste | EU, 2002 | Metaphyseal fractures and cysts, spinal column surgery | Osartis Gmbh & Co. KG, Germany |
| Rapamune® | Sirolimus | oral | FDA, 1999 | Immunosuppressant (mTOR inhibitor) | PF Prism CV |
| Vitoss® | ß-tricalcium phosphate (bioactive device) | i.v. | FDA, 2017 | Resorbable Synthetic Bone Voih Filler/Bone Graft Substitute | Orthovita, Inc. |
| TriCor® | Fenofibrate | oral | FDA, 1993 | Primary hypercholesterolemia or mixed dyslipidemia, hypertriglyceridemia | Abbvie Inc. |
| Vidaza® | Azacytidine (with mannitol powder for reonstitution) | i.v., s.c. | FDA, 2004 | Myelodysplastic syndromes | Celgene |
| Revlimid® | Lenalidomide | oral | FDA, 2005 | Multiple myeloma, Transfusion-dependent anemia, Mantle cell lymphoma (MCL) | Celgene |
| Megace ES® | Megestrol Acetate | oral | FDA, 1993 | Anorexia, cachexia | Endo Pharms Inc |
| Focalin®XR | Dexmethylphenidate Hydrochloride | oral | FDA, 2005 | Attention Deficit Hyperactivity Disorder | Novartis |
| Ritalin® | Methylphenidate Hydrochloride | oral | FDA, 1955 | Attention Deficit Hyperactivity Disorders (ADHD) and Narcolepsy | Novartis |
| Ritalin® LA (Extended release) | Methylphenidate Hydrochloride | oral | FDA, 1955 | Attention Deficit Hyperactivity Disorders (ADHD) and Narcolepsy | Novartis |
| Zanaflex® | Tizanidine Hydrochloride | oral | FDA, 1996 | Spasticity | Covis |
| Invega Sustenna® | Paliperidone palmitate | i.m. | FDA 2006 | Schizophrenia, schizoaffective disorder | Janssen Pharms |
| Ryanodex® | Dantrolene sodium | i.v. | FDA 1974 | Malignant hyperthermia | Eagle Pharms |
| OsSatura™ Dental | Biphasic ceramic (hydroxyapatite/tri-calcium phosphate) | irregular shaped chips (200-2000μm) | FDA 2004 | Bone Grafting Material, Synthetic | IsoTis OrthoBiologics Inc |
| OsSatura™ BCP (Biphasic Calcium Phosphate) | Biphasic ceramic (hydroxyapatite/tri-calcium phosphate) | irregular-shaped chips of different sizes | FDA 2003 | Osteoconductive bone void filler | IsoTis NV |
| NanOss™ Bone Void Filler | Calcium phosphate | pellets | FDA 2005 | Osteoconductive, resorbable, calcium phosphate implant | Angstrom Medica, Inc |
| Beta-BSM, Gamma-BSM, Equivabone | Calcium phosphate | paste | FDA 2010 | Synthetic, biocompatible bone graft substitute | ETEX Corporation |
| Aristada® | Aripiprazole lauroxil | i.m. | FDA 2015 | Schizophrenia (atypical antipsychotic) | Alkermes Inc |
| Avinza® | Morphine sulfate | oral | FDA 1941 (Discontinued) | Severe pain | King Pharms LLC |
| METAL-BASED NANOPHARMACEUTICALS | |||||
| Feraheme™ | Ferumoxytol (Superparamagnetic Iron oxide NPs coated with dextran) | i.v. | 2009 | Iron deficiency anemia | Covis |
| NanoTherm® | Aminosilane-coated superparamagnetic Iron oxide NPs | interstitial administration | Europe, 2011 | Local ablation in glioblastoma, prostate, and pancreatic cancer (intratumoral) | Magforce AG (Berlin, Germany) |
| Venofer® | Iron sucrose | i.v. | FDA 2000 | Iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD) | AM Regent |
| Ferrlecit® | Sodium ferric gluconate complex in sucrose injection | i.v. | FDA 1999 | Iron deficiency anemia (IDA) | Sanofi Aventis US |
| Injectafer® | Ferric carboxymaltose | i.v. | FDA 2013 | Iron deficiency anemia (IDA) | AM Regent |
| INFeD® | Iron dextran | i.v., i.m. | FDA 1974 | Iron deficiency | Allergan |
| Dexferrum® | Iron Dextran | i.v. | FDA 2009 (Discontinued) | Iron deficiency | AM Regent |
| Feridex® | Ferumoxides | i.v. | FDA 1996 (Discontinued) | Magnetic resonance imaging (MRI) contrast media | AMAG Pharms Inc |
| Gastromark® | Ferumoxsil | oral | FDA 1996 (Discontinued) | Magnetic resonance imaging (MRI) contrast media | AMAG Pharms Inc |
| Resovist® | Iron carboxydextran colloid | i.v. | Europe, 2001 | Magnetic resonance imaging (MRI) contrast agent | Bayer Schering Pharma |
| Rienso® | Ferumoxytol | i.v. | Europe 2012 (Discontinued) | Anemia, chronic kidney failure | Takeda Pharma A/S |
| SURFACTANT-BASED NANOFORMULATIONS | |||||
| Diprivan® | Propofol (oil-in-water emulsion in soybean oil/ glycerol/egg lecithin) | i.v. | FDA, 2001 | Monitored Anesthesia Care (MAC) sedation, general anesthesia | Fresenius Kabi USA |
| Cinvanti® | Aprepitant (Emulsion) | i.v. | FDA 2003 | Antiemetic | Heron Theraps Inc |
| Visudyne® | Verteporfin | i.v. | FDA 2000 | Classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis | Valeant Luxembourg |
| Inflexal® V | Inactivated Hemaglutinine of Influenza virus strains A and B | i.m. | 1997 Switzerland | Influenza vaccine | Crucell (Berna Biotech) |
| Estrasorb® | Estradiol emulsion | topical | FDA 1975 (Discontinued) | Menopause (moderate to severe vasomotor symptoms) | Exeltis USA Inc |
| Janssen COVID-19 Vaccine | Recombinant, replication-incompetent adenovirus type 26 expressing the SARS-CoV-2 spike protein | i.m. | FDA 2021 | Prevention of coronavirus disease 2019 (COVID-19) for individuals 18 years of age and older | Janssen Biotech Inc., |