Developing a Topical Adjunct to Injectable Procedures

April 2020 | Volume 19 | Issue 4 | Original Article | 398 | Copyright © April 2020

Published online March 24, 2020

Alan D. Widgerow MBBCH MMed,a,e Melanie D. Palm MD MBA,b Carolyn Jacob MD,c John A. Garruto BS,d Michaela Bell BS MBAe

aDepartment of Plastic Surgery, University of California, Irvine, CA bArt of Skin MD, Solana Beach, CA; University of California San Diego, San Diego, CA cChicago Cosmetic Surgery and Dermatology, Chicago, IL; Northwestern's Fienberg School of Medicine, Chicago, IL dFree Radical Technology, Inc., Oceanside, CA eAlastin Skincare Inc., Carlsbad, CA

Injectable procedures have come to play an enormous part in everyday aesthetic medical practice. Whether its use is directed at volumizing with fillers, decreasing volume using enzymes, skin-tightening using multi-needle approaches, or neuromuscular blockade, the injectable route is the means of delivery in all these cases, making injectable procedures the most common aesthetic procedure performed. As with all procedures, expected and unexpected consequences may follow including bruising, swelling, discomfort, and the possibility of infection. This paper outlines the scientific process and validation of a product designed as an adjunct to injection therapy and the scientific deep dive needed to encompass both symptomatic and adjunctive purposes. On the symptomatic side, bruising, swelling, and pain were considered, while volumetric enhancement, regeneration, and anti-microbial/biofilm effects were desired outcomes from the adjunctive perspective. Utilizing peptides and active agents aimed at reducing excess residual iron and stimulating macrophage absorption of red blood cells, we were able to achieve efficient resolution of bruising. In addition, peptides were included to stimulate collagen, elastin, and hyaluronic acid in synergy with the injectable. Anti-inflammatory, antimicrobial, and antibiofilm agents were added to aid in the safety profile of the injectable. In vivo testing of bruising resolution demonstrated that at day 2/3, participants using the study product (INhance Post-Injection Serum with TriHex Technology®, Alastin Skincare, Inc. Carlsbad, CA) had 73% less bruise color intensity and statistically significant improvement over the bland moisturizer. Overall, 81% of subjects applying the study topical product had less bruising at day 2/3 compared to the bland moisturizer.

J Drugs Dermatol. 2020;19(4): doi:10.36849/JDD.2020.5016



Every invasive surgical procedure from the simplest injection to the more complex surgical procedure creates the potential for bruising and swelling. Even newer techniques such as cannula delivery of injectables still require needle introduction for the portal site, and the cannula itself may still cause a bruise. Bruising is a result of extravasation of red blood cells (RBCs) into the tissue. Once outside the vascular system, RBCs quickly burst, releasing free hemoglobin (Hb) that is prone to oxidation states that have potent pro-inflammatory and pro-oxidant effects.1 The heme that is released is phagocytized by macrophages. Following internalization by the macrophage, heme is cleaved into biliverdin, carbon monoxide, and iron. This mechanism not only provides effective elimination of Hb, but it also assures iron recycling for new erythropoiesis.1 However, leaving the byproducts of bleeding around for too long creates the risk of the pro-inflammatory effects mentioned above that can interfere with wound healing, promote pigmentation and (of course) look very unsightly in addition to representing an obvious sign of injection or surgery. In addition, delayed bruising accompanying filler injections has recently been attributed to the hyaluronic acid structure closely resembling that of heparin and behaving in similar ways in certain situations. 2 Sometimes bruising cannot be avoided, and no topical agent currently available can prevent it; nevertheless, there is a way of accelerating bruise resolution by removing by-products of RBC extravasation more efficiently.

A bruise typically appears hours after injury to the tissues just below the skin’s surface or even sooner (occasionally instantly) if a blood vessel is breached during a procedure. RBCs seep into the surrounding tissue and macrophages begin to break down the cells that rapidly lose oxygen giving them a bluish hue. The byproducts of hemoglobin breakdown (heme, biliverdin, bilirubin, hemosiderin) transmit the various colors to the skin that slowly resolve once these pigments are absorbed by the macrophages and digested, known as blood product accumulation. This process can vary from days to weeks depending on the degree of accumulation of blood products. The testing that follows was conducted to determine whether lactoferrin, phosphatidylserine, and selected peptides can enhance the process of phagocytosis and improve the functionality of macrophages.