Introduction
Laser-assisted drug delivery is highly efficient with topical treatments for various conditions. Currently, LADD is offered in combination with photodynamic therapy and corticosteroid treatment. Laser-assisted drug delivery is attempted only after all the first-line therapies fail to treat.
In LADD, the heat from the laser pierces the natural barrier producing microscopic pores in the skin and providing direct access to the underlying skin. When a topical drug is applied over this laser-treated surface, the pores facilitate faster and greater drug delivery and deposition. The increased drug deposition increases the healing process.
What Are the Types of Lasers Used in LADD?
Different types of lasers are used for LADD. Each type is more or less active, with a different safety profile.
Practically, the lasers used in LADD are divided into four groups:
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Fully ablative lasers use water as chromophores, heat it, and vaporize the skin. For this, the carbon dioxide (CO2) laser (10,600 nm) or the erbium-doped yttrium aluminum garnet (Er: YAG) laser (2,940 nm) are used.
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Ablative fractional laser (AFL), the same as the previous group, causes thermal injury in the microscopic treatment zones when used fractionally.
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Non-ablative fractional laser (NAFL), similar to the previous group, includes erbium fiber laser (1,550 nm).
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Non-ablative dermal remodeling lasers.
What Are the Factors That Influence Drug Application?
When applying topical drugs directly on the skin surface, these factors are taken into account.
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The biocompatibility of the drug for topical application.
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Uninfected, sterile environments for the application of LADD procedures.
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The interval between laser use and topical application of the product on the skin. The microscopic channels in the surface close over time with remaining debris like fibrin, inflammatory cells, and keratin deposits.
Topical application six hours after use of the laser increases drug absorption, with a high success rate during the first 30 minutes. However, no changes in absorption are seen when the drug is applied after 24 hours.
What Are the Indications for LADD?
The following are the drug that showed better results when combined with LADD:
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Aminolevulinic acid and 5-MAL laser-assisted PDT - actinic keratosis, fine nodular basal cell carcinoma (< 2 mm), superficial squamous cell carcinoma.
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Triamcinolone acetonide (TCA) - Hypertrophic and keloid scars.
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Ingenol mebutate - Bowen disease.
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5-Fluorouracil - Superficial basal cell carcinoma and Bowen's disease on the trunk and limbs < 2 cm.
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Timolol - Deep infantile hemangioma.
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Pimecrolimus, Tretinoin, and Bimatoprost - Hypo pigmented scars.
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Poly-L-lactic acid - Atrophic scars.
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Finasteride - Male pattern baldness.
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Vitamins - Recovery after rejuvenation treatment with ablative fractional laser.
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Anesthetics - Absorption of and pre-exposure to subcutaneous injections.
What Are the Other Applications of LADD?
LADD is used to introduce drugs into the body for many reasons, including dermatologic application. The efficiency of fully ablative and fractional lasers in introducing small interfering RNA molecules (siRNA) and antibodies can prevent the conversion of various genes and has been useful in many diseases. Using siRNA with microRNA in psoriasis patients can be a more effective treatment option. LADD has been effective in producing a favorable immune response with topical vaccines. Advanced studies with stem cells that produce blood cells applied topically in combination with ablative lasers pave the way for using LADD as an alternative treatment option in hematopoietic progenitor transplant.
What Are the Challenges in LADD?
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Practical factors include equipment cost and access to laser and light-based devices.
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Operator factors like training and experience in laser technology, inconsistencies in treatment protocol, laser channel depth, and density.
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Drug factors are the potential for systemic toxicity, absorption variability, and drug dosing unpredictability.
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Patient factors like FitzPatrick skin type and its response to laser or drug, anatomical treatment area and its effect on drug absorption, induction of localized and systemic hypersensitivity.
What Are the Safety Protocols When Using LADD?
Laser Considerations:
Any radiation can risk human tissue. Fully ablative lasers cause tissue heating and vaporization increasing the risk of burning, scarring, and pigmentation. The possibility of laser-induced redness, swelling, scab, blister, scar, and pigmentary changes do exist with LADD, particularly at higher stimuli and treatment densities. As the blood coagulates during the treatment, topically applied drugs may be released, thereby increasing the risk of local and systemic reactions. Therefore, laser settings must be designed cautiously to maximize the benefit and minimize the risk.
Characteristics of the Drug:
Targeting drugs through the hair follicles increases the penetration and absorption of drugs applied to hair-bearing areas. Therefore, LADD performed in these areas should be done carefully, as the effect on hairless skin differs from hair-bearing skin. The anatomical site, local skin enzymatic activity, skin integrity, water content, acidity, obstruction, and patient age also play significant roles in drug penetration and its side effects. For instance, inflamed and compromised skin absorbs drugs more readily than unbroken, healthy skin; moist skin absorbs ointments and creams more effectively than dry skin; aged skin may act differently to topical drugs than younger skin.
Local Skin Reactions:
LADD increases the accumulation of topical drugs on the skin, treating various skin conditions, including cancer, scars, and skin damage due to sunlight. However, the accumulation of drugs within the dermis of the skin may lead to a local drug reaction. It is common after fractional AFL-assisted PDT. Patients present with increased burning sensation, redness, pain, swelling, crusting, pruritus, purpura, and temporary pigmentations. The long-term local skin effects include inducing DNA damage.
Systemic Reactions and Toxicity:
LADD is combined with the cautious systemic delivery of analgesics, anti-cancer medications, and bone marrow cells. This is in harmony with improved drug delivery through laser-created pores or channels that raise the fear of systemic toxicity, particularly when treating larger skin areas. Finally, physicians should be mindful of the systemic side effects and toxicity of all drugs with which LADD is attempted. Hence, with an identified treatment area and assuming the absorption level of a standard dose in that area, the clinician can administer the drug so that any systemic absorption will be within the beneficial and safe range.
Conclusion
Topical treatment with LADD allows higher penetration and absorption and produces better results by achieving a synergistic effect between drugs and lasers. Safety and the most suitable technique remain debated, although undoubtedly that these disputes will gradually be resolved in the upcoming years.
