The Journey Of Botox — From Injections To Creams

Dr. Shazia Ali
Botox has proven its success in combating dynamic wrinkles and has acquired a star status among anti-aging treatments during the past 25 years. Originally approved for the treatment of eye muscle disorders like blepharospasm and strabismus, Botox over the years has become an increasingly popular cosmetic procedure. According to the American Society of Plastic Surgeons (ASPS), botox (BoNTA) injections were the single most popular minimally invasive cosmetic procedure performed in the United States in 2015. The ASPS report found that 7.3 million injections were given in 2015, showing 3% rise from the year prior.

The Not So Glam Side Of Botox
Although cosmetic BoNTA has demonstrated strong efficacy and good safety profile, but adverse events do occur from time to tome. Misplaced injections, unique anatomy of patients and novice doctors doing the treatment can lead to unwanted effects in non-target areas. Looking at the literature reviews side effects like eyelid and brow ptosis and partial lip ptosis have been reported after injection of BoNTA into the upper face and periocular areas, respectively. Few reported cases of injection into the pretarsal portion of the orbicularis oculi muscle have resulted in dry eyes. There have also been reported complications involving pupillary reactions and light sensitivity in some cases.

Additionally limitations of using injections include pain, erythema, swelling, bruising, tenderness, and potential infection from needle use.

The patient’s medical regimen is in selected cases potentially affected by being advised to avoid aspirin, nonsteroidal antiinflammatory drugs, and vitamin E before injection to reduce the risk of bleeding and bruising. Bruising is of particular concern in the lateral canthus and orbicularis oculi region, where the blood vessels are superficial and the skin is thin.

Next Step In Evolution

Research conducted among consumers has shown that many consumers are needle averse and would prefer a more noninvasive alternative that would provide the same benefits as BoNTA injections. The survey showed that in US alone 11 million people are potential target demographic for BoNTA treatments, but less than 10 percent have actually received treatment. Providing an alternative non-injectable option to current injections holds the potential to expand the market considerably.
Dr. Shazia ali
The target consumer market can be organized into the following three categories:
1) Past users of BoNTA injections who would like a less painful, and cheaper option
2) Consumers with no past history of injections because of the expense and/or pain associated with them and
3) Consumers currently undergoing regular injections who would welcome a more comfortable way to maintain each treatment

A safe, targeted alternative in the form of topical BoNTA makes an attractive option.

Nanoparticle Technology & BoNTA Cream

Nanotechnology allows the potential to deliver molecules into the skin, which ordinarily do not penetrate the superficial corneal layer. This ability to enhance penetration of active ingredients offers many benefits. In the last decade two companies, Transdermal Corp., Birmingham, Michigan, and Revance Therapeutics, Newark, California, have made good progress on topical delivery of BoNTA sharing their clinical trials.

Dr. Shazia Ali

Transdermal Corp. was formed in August 2008, since then it has developed an FDA-approved topical BoNTA cream based on commercially viable ionic nano-particle technology (InParT™). This technology consists of micelles (surfactants and protein solubilizers), coated with lipid molecules that entrap the active component with no changes in chemical composition - the particles are one to ten nanometers in size; smaller than skin pores.

This transdermal noninvasive drug delivery technique preserves the bioactivity of molecules without denaturing them. The cream (CosmeTox) contains BoNTA and is intended for the softening of facial rhytides as well as reduction in hyperhidrotic (excessive sweating) conditions. Active ingredients in the cream allow for greater toxin stability at room temperature for extended periods of time.

How Does It Work?
Topical BoNTA allows for deeper delivery of the active molecules into the skin in order to encourage the same effect of injected BoNTA — inhibiting the release of Acetylcholine and blocking neuromuscular transmission. The stabilized toxin cream is applied topically onto the skin and dosed by the quantity of cream applied. Using nanospheres and absorption enhancers, the toxin is delivered into the skin without any known skin damage or systemic toxicity. The cream also behaves in a similar fashion as an injectable in that when it is applied, it stays local for targeted delivery.

A study was conducted in 2008 to test the efficacy of this topical BoNTA cream (CosmeTox) on facial wrinkles. The study involved 4 to 7 weeks of treatment with 12 weeks of follow-up evaluation. Within the first two weeks of treatment, the BoNTA group reported subjective improvements in their appearance, including less wrinkling, but also noticed a fading of dark circles under their eyes as well as a hyperpigmentation reduction in treatment areas. The active ingredient cream was compared to a placebo on 40 female subjects. The active ingredient cream contained a concentration of 2U/mL BT and the vehicle control contained no BT. They were assessed by Facial Line Outcomes and Self Perception of Age questionnaires. The Facial Lines Outcome scores were improved and maintained for the duration of the study period of almost three months. The Self Perception of Age was also reduced in the majority of subjects. At Week 4, more than 85 percent of the BoNTA cream group rated their wrinkles as improved by at least 75 percent.

RT001 Botulinum Toxin Type A Topical Gel Revance Therapeutics, Inc., Newark, CA contains an albumin-free 150-kDa BoNTA and a novel peptide that enables transcutaneous delivery of the BoNTA.  RT001 raised a lot of hopes with successful Phase 2 trials.

Two efficacy scales — the Global Assessment of Lateral Canthal Line Severity and the Patient Severity Assessment — have been used in phase 2 research to quantify the degree of muscle rest achieved (the primary end point). To be categorized at the most stringent level of efficacy, it was necessary for physicians and patients to record a crow’s feet severity reduction of at least 2 points in their respective rating systems.
Dr. Shazia Ali

Investigators with a 90-patient study enrolled participants at 3 sites, and randomized them to active treatment or placebo for a single treatment of RT001. A reduction in severity of 1 point was demonstrated in 89% of the RT001 group and 28% in the control group (P < .0001). A reduction of at least 2 points was demonstrated in 44% of the RT001 group and in 0% of the control group (P < .0001).


Phase 3 Trial – REALISE 1
The Phase 3 trial was a randomized, double-blind, parallel-group, placebo-controlled study to evaluate the safety and efficacy of DaxibotulinumtoxinA Topical Gel (RT001) for the treatment of moderate to severe lateral canthal lines.  A total of 450 adult patients were enrolled at seven sites in the United States and were randomized 1:1 to a single treatment of either RT001 or placebo topical gel applied to lateral canthal lines on both sides of the face using Revance’s proprietary applicator.
In a press release Dan Browne, President and Chief Executive Officer at Revance announced that, “We are disappointed with the results of the REALISE 1 trial. The data was unambiguous, and we do not plan to continue development of RT001 topical for crow’s feet. Based on these results, we have also decided not to pursue the current clinical development plan for RT001 in axillary hyperhidrosis.  We are grateful to all the patients and investigators for their participation in the REALISE 1 trial.” As of today the development of tropical botox RT001 has been shelved by Revance after non satisfactory Phase 3 trial  and long acting  DaxibotulinumtoxinA for Injection (RT002) has entered phase 3 trials.”

The Future

Delivery Of Botox Using Iontophoresis
Dr. Shazia Ali
Iontophoresis is a drug delivery system that uses a small external electric current to deliver water-soluble, charged drugs into the skin. A  case report published in the British Journal of Dermatology has shown that iontophoresis might enhance botox uptake by the sweatglands while treating cases of palmer hyperhidrosis.

Delivery Of Topical Botox Enhanced by Fractional CO2 Laser:
As previous studies have demonstrated that topical surface application of BoNT A has negligible cutaneous bioavailability and is not effective in treating wrinkles. A new study was designed to determine the effect of BoNT a solution applied topically on the skin surface immediately after ablative fractional CO2 laser treatment. There was a clinically significant greater degree of improvement in wrinkles after treatment with CO2 laser, on the topically applied BoNT A side. Also, the difference between the 2 treatment types (laser followed by topical BoNT A vs laser followed by saline) at 1 week and at 1 month was statistically significant.

Another study evaluated the synergistic efficacy and safety of combined topical application of Botulinum Toxin Type A (BTX-A) with fractional CO2 laser for facial rejuvenation. Twenty female subjects were included for this split-face comparative study. One side of each subject's cheek was treated with fractional CO2 plus saline solution, and the other side was treated with fractional CO2 laser plus topical application of BTX-A. Patients received one session of treatment and evaluations were done at baseline, one, four, and twelve weeks after treatment. BTX-A combined with fractional CO2 laser sides showed higher physician's global assessment score, subject satisfaction score, roughness, skin hydration, and skin elasticity compared to that of fractional CO2 plus saline solution side at 12 weeks after treatment.

Considering the non chemoimmobilization effects of botox and its role in anti scaring and rejuvenation it will remain a potential area of research. The newer non-invasive delivery modes of Botox will be explored further in the future.


Silky Smooth And Hair-free Skin – Guidelines For Using Epilators

Epilation, Braun, Silk Epil 9, hair removal
Body hair removal is an integral part of every girl’s beauty routine. There are many techniques to get rid of body hair. Shaving is arguably the most popular, but its main drawback is that the hair grows back real quick and you need to shave 2-4 times per week (depending on how smooth you wanna feel). Balancing school, work, family, friends and robust social life no one has time to chase hair stubble on daily basis. Hence a more effective technique called epilation has become popular among the astute ladies who value silky smooth skin 27/7 all year round. Epilation involves ripping out the hair from the root and delivers hair-free skin for weeks. Under the epilation umbrella we have plucking, threading, waxing, halawa and mechanical epilation devices (which use multiple battery-operated tweezers that work simultaneously to give expeditious hair removal with weeks of hair-free skin).  

Mechanical epilation is practically as quick, easy and convenient as shaving. It keeps you hair-free for weeks to follow and that is why it has become positively popular with the ladies. When it comes to epilaton devices all epilators are not created equal, some use more advanced technology and deliver superior results with less pain and discomfort compared to others. After trying many, my favorite happens to be Braun Silk Epil 9.

Epilation With Braun Silk Epil 9
Braun Silk Epil 9
Silk epil 9 is the culmination of advanced technology that takes epilation to new heights of precision and comfort. Braun has incorporated years of epilation experience and made sure SE9 takes care of hair removal like no other device in the market can.  Lets get you introduced to Braun SE9:

Suitable For All Over Hair Removal: Braun SE9 is designed for use on your face, underarms, arms, legs and bikini area and it has different attachments to cater to different areas of the body. In the packaged box you have a shaver head, trimmer cap, high frequency massage cap, skin contact cap, facial cap and a charger. One device multiple uses, it doesn’t get better than this. Braun has studied the epilation process in depth, listened to the user needs and made sure that their consumers get the best and most comprehensive experience with SE9.
Braun Silk Epil 9
Plucks Even The Shortest Of Hair: Braun SE9 uses new patented MicroGrip Technology with 40 tweezers, which Features wider, longer and deeper tweezers that remove hair with ultimate precision. Even the shortest hairs (down to 0.5mm) that wax or other epilators can’t catch can be easily plucked away with Braun SE9. With this new feature you don’t have to wait for your body hair to grow long enough for waxing or epilation with other devices.
even short hair can be plucked
Faster Hair Removal Sessions: The ergonomic head of the Braun silk epilator 9 is 40% wider than any other model Braun has ever made which makes the hair removal sessions very fast and quick. If you’re doing both your legs and arms it takes around 10-15 minutes from start to finish.

Pain Management: The skin comforting pulsating action of the Braun SE9 is one of the most loved feature by all users. High frequency massage cap with pulsating active vibrations helps deliver an extra gentle epilation experience. The pulsating motion mechanically massages your skin to distract your nerves as the micro grip tweezers pluck hair making the epilation process a lot more comfortable. Anyone who has tried epilation knows plucking hair from the roots is a painful experience, but his feature helps reduce the pain factor by many folds. Braun SE9 also comes with cooling ice packs as an additional accessory for reducing pain during and after the session.

Braun SE9 is 100% waterproof. The underwater epilating function really helps to reduce the pain in sensitive areas like the bikini or underarm area.  This feature also saves a lot of time and effort spent to clean up your removed hairs after the session.

Keeps In-Grown Hair At Bay: If you combine the exfoliation head with the massage function you will be able to buff off dead skin and deal with the problem of potential in-growing hairs. This function alone makes this epilator a premium epilator.

Guidelines For Perfect Epilation
Guidelines for perfect epilation
Prepare The Skin: Be sure to clean the skin before you epilate. If you choose the dry epilation, take a shower and dry your skin well with a towel in the opposite direction of hair growth. The hair will stand up, making it easier to be plucked out by the tweezers.

If you choose the wet epilation, you should stay at least ten minutes in the shower/bath to let the hair pores to open.

Exfoliate Before Epilation: This not only helps your skin to regenerate faster but also makes it smooth and prevents ingrown hairs, by bringing them to the surface, to be plucked out by the epilator more easily. Another reason behind this important step is, that it will clean the skin of its natural oils and open the pores creating a less painful epilation. Some people exfoliate just before epilation, but if you have sensitive skin, its much better that you should do this operation a day before.
Right Length Of Hair For Epilation: The recommended hair length for ideal results with epliation for Braun SE9 is between 0.5mm to 2mm. If your hair length is too long, you will feel more discomfort and the epilator won’t be able pull out the hair from the root efficiently, with a chance of pulling and breaking hair. For a prime experience trim hair to the right length prior to the epliation. Braun SE9 epilators come a trimmer cap, specially created for these situations or if you just wants only to trim a certain area; like the pubic area, instead of epilation.

Epilation Step One: Charge the epilator in advance, as SE9 can only be used cordless, you can’t use it while charging. If you want the best results, you should make sure that your epilator is charged and ready to use it at its full capacity. Braun SE9 epilators operate at two-speed levels. You should always start with the lower speed and move to the higher speed when you feel that you are ready and comfortable.
Wet or dry option: Choosing the wet alternative will make the entire experience less painful and more effective. Warm water opens the pores and the hair can be plucked from the root more easily. Some ladies prefer the dry epilation, as the hair doesn't stick to the skin and it can be removed faster.

Hold The Epilator Correctly And Use It Properly: Keep the epilator at a 90-degree angle to the skin. Braun SE9 comes with a pivot head, which follows the curves of the body to remove hair more efficiently. You don't need to press it too hard on the skin because doing so can irritate, scratch or pinch your skin. Gently hold it against your skin and glide against the direction of hair growth for best results with minimum pain. Another trick that can make the epilation process more smooth and painless is holding your skin taut with your free hand while you’re gliding the epilator over your skin. Together with this motion, use small circular motions to catch all the hairs because all hair don’t grow in the same direction. By making small circular movements you can catch even the “rebel” hair.

how to use epilator

Work In Small Areas: Don't make multiple passes, if it isn't necessary. In order not to irritate your skin, you should epilate on small surface areas. Work slowly, without rushing the process, if you want to see the best results. Working on small areas is ideal because you can catch most hair, without missing any and you won't irritate the skin.

Best Time To Epilate: Most ladies prefer epilating at night. Epilation at night gives the skin time to calm down for few hours, so the red bumps on the skin in the morning are less apparent and you can wear a dress or skirt with more confidence without worrying about the redness and bumpy skin.
Post Epilation Skincare: After epilation, you should apply a moisturizing cream, which will soothe and hydrate the skin.  Some people use hydrocortisone 1% cream to calm the skin down, helping to reduce redness and bumpiness.

Keeping Skin Permanently Smooth: After epilation you should have smooth skin for almost 4 weeks, but as you all know that hair grows in stages and some hairs will appear much sooner than you have expected. To keep skin permanently smooth you should plan in-between touch-up sessions that will take fraction of time compared to the full body session. Plus you know now that when you pluck shorter hair it delivers better results with less pain during epilation.
Keep Your Epilator Clean: It is vital that you clean your epilator correctly post-use. Gently clean the dry epilator attachments with the brush that comes with the kit, to remove the hair and dead skin cells. For the wet epilation, dab them dry with a clean towel, then clean with the brush. Hygienically speaking, it's not recommended to share your epilator with other people, even though is your life partner.

Cleaning your Braun Silk Epil 9 Epilator

Reality Check: Don't confuse epilation with the permanent hair removal methods, like laser/IPL or electrolysis. Although some users have admitted that their hair grow less in certain body areas, the reality is that if you let your hair grow back without epilating or waxing, it will grow back exactly as it originally was; thick, long, dense or fine, as you inherited it.