Journal of Nanomedicine & Nanotechnology

Targeted Site-Specific Therapeutics for COVID-19

Iversen P, Porter TR and Kipshidze N^* MPH, Clinical and Public Health Researcher, Cardiac Implants LLCNew York University, New York, USA
^*Correspondence: Kipshidze N, MPH, Clinical and Public Health Researcher, Cardiac Implants LLCNew York University, 620 E. 20^th Street, Apt 3H, New York, NY 10009, USA, Tel: 9173706247, Email:

Received: 29-Apr-2020 Published: 17-Jul-2020, DOI: 10.35248/2157-7439.20.11.548

Perspective

At the time of this letter there are no definitive therapies for COVID-19. The early negative results based on small, underpowered, non-controlled studies and just few open label RCT’s are discouraging. Moreover, one study noted that an even higher dose than what was administered may be required to achieve therapeutic efficacy [1]. However, almost all the proposed pharmaceutical therapies for COVID-19 pose at least a few possible adverse effects. Targeted drug delivery of these promising pharmaceuticals might prove to be more effective, enhancing the local effect while attenuating their off-target side effects [2]. SARS-CoV-2 has an affinity for two host cell factors, which are primarily expressed in human lung tissue: ACE-2 and TRMSS2 [3,4]. Considering that COVID-19 primarily affects the lungs in patients with ARDS [5] we propose a targeted drug delivery strategy using different types of drug delivery vehicles such as nano-particle drug carriers, liposomes, viral vectors, perfluorocarbon droplets, and microbubbles. The latters also adheres to sites of damaged vascular endothelium and thus may be a method of systemically targeting delivery of therapeutics to damaged lungs with SARSCoV2. For example, perfluorobutane gas microbubbles (PGMC) with a coating of dextrose and albumin efficiently bind to different pharmaceuticals. These 0.3 μm to 10 μm particles bind to sites of vascular injury [5]. Further, the perfluorobutane gas is an effective cell membrane fluidizer. The potential advantages of microbubble carrier delivery include none to minimal (additional) vessel injury through delivery, no resident polymer to degrade leading to eventual inflammation, rapid bolus delivery, and repeated delivery. Microbubble carriers were successfully used in different animal models and clinical trials to deliver antisense oligonucleotide and/ or Sirolimus to the injured vascular bed [6-8]. The formulation of microbubbles and therapeutics is easy and can be performed in a hospital pharmacy settings, considering they are currently used widely to enhance diagnostic ultrasound imaging [9]. Given the growing evidence that the most detrimental SARS-CoV-2 reactions are primarily within the respiratory system, localized targeted delivery of therapeutics may prove advantageous over a systemic approach, provided that bioavailability to the target tissue can be proven/verified.

REFERENCES

1. Cao B, Wang Y, Wen D. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020.
2. Rismanbaf A, Zarei S. Liver and Kidney Injuries in COVID-19 and Their Effects on Drug Therapy; a Letter to Editor. Arch Acad Emerg Med 2020; 8:e17.
3. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203: 631-637.
4. Hoffmann M, Kleine-Weber H, Schroeder S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020.
5. Tsutsui JM, Xie F, Cano M, Chomas J, Phillips P, Radio SJ, et al. Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction. J Am Coll Cardiol 2004; 44:1036-1046.
6. Wang W, Xu Y, Gao R. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020.
7. Porter TR, Xie F, Knapp D. Targeted vascular delivery of antisense molecules using intravenous microbubbles. Cardiovasc Revasc Med. 2006; 7(1): 25-33.
8. Kipshidze NN, Porter TR, Dangas G. Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model. Catheter Cardiovasc Interv 2005; 64(3): 389-394.
9. Porter TR, Mulvagh SL, Abdelmoneim SS, Becher H, Belcik JT, Bierig M, et al. Clinical Applications of Ultrasonic Enhancing Agents in Echocardiography: 2018 American Society of Echocardiography Guidelines Update. J Am Soc Echocardiogr 2018;31:241-274.