Laser-assisted drug delivery (LADD) is a drug delivery technique commonly used in the dermatology field that involves lasers. As skin acts as a protective barrier to the environment, the absorption of topical products through the epidermis is limited; thus, different drug delivery modalities have been employed to improve the efficacy of these treatments. The use of lasers in LADD has been shown to enhance the penetration of drugs transdermal, leading to a higher absorption rate, limited systemic effects, and reduced duration of treatment. Although this technique has evolved in the past decade due to its efficacy through scientific research and clinical practice, there remain some limitations regarding the safety aspect that needs to be taken into consideration.
Transdermal drug delivery
The skin barrier
Skin is the largest organ in the human body that acts as the primary protective barrier against the external environment. It provides protection against ultraviolet light, trauma, pathogens, microorganisms, and toxins, sensory perception, temperature regulation, and immunity. There are primarily three layers of skin, which include the outer epidermis, followed by the dermis and subcutaneous tissue, or hypodermis. Skin is used as the target for drug delivery as it is a convenient route of drug administration, and the large area allows for different placements on the skin for transdermal delivery
Transdermal delivery Transdermal delivery is a non-invasive method commonly assisted in transporting topical products into intact and healthy skin. The substances initially penetrate through the stratum corneum, which is the outermost layer of the epidermis, then diffuse into the deeper epidermis and dermis layers for a systemic effect. Although transdermal drug delivery presents several advantages as compared to other conventional modalities such as oral and parenteral routes, the complexity of the skin barrier limits the methodology to reach its full potential.
Improvement in transdermal delivery
Various technologies have been developed to enhance the permeability of transdermal drugs, which can be divided into passive or chemical and active or physical methods. The passive approach involves the optimization of drug and vehicle interaction that could modify the stratum corneum structure or the addition of penetration enhancers for better absorption rates. Some of the limitations of this approach include lag time in drug release, low efficiency, and skin irritation. The active approach involves ultrasound, electrical stimulation, thermal approach, and mechanical approach. These techniques facilitate the transportation of drugs by using energy as a driving force. Within the thermal approach, laser-assisted drug delivery is a common and effective method that has been used to increase the efficiency of transdermal drug delivery by selectively destroying the chromophores of interest using light waves.
Specifications for using LADD
Lasers
There are different types of lasers used in LADD, and they can be categorized into four main groups: (1) fully ablative lasers, (2) ablative fractional lasers (AFL), (3) non-ablative fractional lasers (NAFL), and (4) non-ablative dermal remodeling lasers. Common fully ablative lasers, including carbon dioxide (CO2, wavelength peak 10,600 nm) and erbium-doped yttrium aluminum garnet (Er:YAG, wavelength peak 2940 nm), target water as their chromophore where all water-containing tissues within the epidermis are ablated. With its high wavelength peak, CO2 laser has a high absorption rate of water and adipose tissues; whereas the wavelength of Er:YAG allows for the precise ablation of water and minimizes heat generation. The mechanism of AFL is similar to fully ablative lasers but when used fractionally, they create multiple vertical columns on the skin surface, which are also called microscopic treatment zones (MTZ) and allow for a more quantitatively controllable usage in LADD. NAFL are also fractionated lasers that produce MTZ, but as they are non-ablative, there is no ablation of the epidermis and instead, they use light energy to damage the dermis layer. Non-ablative dermal remodeling lasers include all types of lasers with a chromophore that is different from water as used in the previous groups. Common lasers within this group are neodymium-doped YAG laser (Nd: YAG, wavelength peak 1064 nm and 1320 nm), pulsed dye laser (wavelength ranges from 585 to 600 nm), and intense pulsed laser (IPL, wavelength ranges from 500 to 1200 nm). In general, with its high efficiency and rapid recovery time, AFL is the more common modality used for LADD, especially in the dermatology field.
Drugs Lipophilic substances have shown to have a greater ability to cross the epidermis, thus, the efficiency of LADD is more remarkable when using hydrophilic substances. Liquid and gel formulations of drugs also are proven to cross the channels created from the fractional lasers more easily as compared to oily formulations such as creams or ointments. Common drugs used in LAPP include but are not limited to 5-aminolaevulinic (5-ALA), 5-aminolevulinate (MAL), methotrexate (MTX), imiquimod, 5-fluorouracil (5-FU), timolol, triamcinolone acetonide (TAC), bimatoprost, tretinoin, pimecrolimus, poly-L-lactic acid (PLLA), analgesics, minoxidil (MXD), diphencyprone (DPCP), vitamin C, small interfering RNA (siRNA), vaccine, and antibodies.
Patients The efficiency of LADD with the selected laser settings is dependent upon the different characteristics associated with individual patients. The dermatological condition, the properties of the skin, and the surface area are taken into consideration to determine the eligibility of the patients for certain lasers and provide optimal treatments for each patient. For example, hydrated skin has a higher affinity for absorption of oily substances; skin atrophy that is associated with solar elastosis is more likely to produce pathological scarring under high laser intensity; hair areas have a higher absorption rate; older patients are more prone to adverse effects such as atrophy, erosion, ulceration, and will require longer recovery time. Not all patients are candidates for LADD as this method is intensified as compared to conventional topical treatment.
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