As a classic exfoliant and antibacterial ingredient, salicylic acid antibacterial solution is widely used in the fields of skin infection and acne treatment. However, its bactericidal efficiency depends not only on concentration and duration of action, but also on the drug's ability to penetrate into the biofilm and tissue layer. Studies have shown that insufficient permeability may lead to drug enrichment in the surface layer of the lesion and inability to kill deep pathogens, while excessive permeation may cause systemic toxicity. This article will analyze the intrinsic relationship between permeability and bactericidal efficiency from the aspects of drug delivery mechanism, pathological environmental influence and synergistic strategy.
Salicylic acid antibacterial solution exerts its antibacterial effect by dissociating bacterial cell membrane phospholipids, inhibiting bacterial enzyme activity and interfering with DNA synthesis. Its penetration pathways mainly include: 1) intercellular lipid pathway: diffusion through the intercellular lipid bilayer of the stratum corneum; 2) hair follicle sebaceous gland pathway: penetration into the sebaceous gland unit through the hair follicle opening; 3) intracellular pathway: transmembrane transport through keratinocytes. Among them, lipophilic non-dissociated salicylic acid is easier to penetrate the lipid barrier, while the dissociated type is conducive to diffusion in an aqueous environment. Studies have shown that when the pH value is 4.0-5.5, the dissociation degree of salicylic acid is moderate, which can not only maintain a sufficient non-dissociated ratio to promote penetration, but also maintain an effective antibacterial concentration.
For follicular sebaceous gland infections caused by Propionibacterium acnes, salicylic acid needs to penetrate deep into the hair follicles to work. In vitro experiments show that when the penetration depth reaches the funnel of the hair follicle (about 200-300μm), the bactericidal efficiency is 40%-60% higher than that of only acting on the epidermis. This is because the drug needs to break through the keratin plug and sebum layer to contact the pathogens parasitic in the hair follicles.
In skin trauma infections, Staphylococcus aureus may invade the dermis or even the subcutaneous tissue. At this time, the penetration depth of salicylic acid needs to reach 1-2mm to effectively kill bacteria. Studies have found that when permeability is insufficient, the concentration of drugs in the dermis is only 1/5-1/3 of that in the epidermis, resulting in the continued survival of deep bacteria and easy recurrence.
The liposome-encapsulated salicylic acid antibacterial solution has a 2.3-fold higher penetration rate than traditional aqueous solutions, and the microemulsion formulation can increase the accumulation of drugs in the stratum corneum by 3 times. This is because lipid carriers can fuse with stratum corneum lipids to promote transmembrane transport of drugs.
When the pH increases from 3.0 to 5.5, the permeability coefficient of salicylic acid in pig skin increases from 0.23×10⁻³cm/h to 1.02×10⁻³cm/h. However, too high a pH (>6.0) will lead to an excessively high proportion of dissociated forms, which will reduce the drug's lipid-soluble permeability.
Within a certain range (0.5%-5%), the higher the concentration, the greater the permeation driving force. However, when it exceeds 5%, the drug may form crystals in the stratum corneum, hindering further penetration and reducing the bactericidal efficiency.
In chronic infection sites, bacteria often form biofilms to protect themselves. If the drug cannot penetrate deep into the biofilm, it can only kill surface bacteria, leading to repeated infections. Studies have shown that bacteria inside biofilms are 10-1000 times more tolerant to drugs than planktonic bacteria.
Insufficient local drug concentration can induce bacteria to produce efflux pumps or change membrane permeability, which can lead to the emergence of drug-resistant strains in the long term. For example, the formation of methicillin-resistant Staphylococcus aureus (MRSA) is closely related to insufficient drug penetration.
Increasing the frequency or concentration of medication to compensate for insufficient permeability may cause skin irritation, which in turn reduces patient compliance and prolongs the treatment cycle.
Solid lipid nanoparticles (SLN) can deliver salicylic acid to the dermis, increasing the concentration of the drug in the dermis by 5 times compared to free drugs. Nanoemulsions can carry drugs through the dense stratum corneum, increasing the bactericidal efficiency of Propionibacterium acnes by 3 times.
0.5% azone can increase the penetration of salicylic acid in the skin by 2.8 times, and 1% laurocaprolactone can increase the penetration rate of the drug by 4 times. Its mechanism is to increase the drug diffusion channel by destroying the lipid arrangement of the stratum corneum.
Iontophoresis can increase the penetration of salicylic acid by 6-8 times. The microneedle array forms a micron-level channel in the epidermis by mechanically puncturing the stratum corneum. The drug penetration depth can reach more than 1mm, significantly enhancing the bactericidal effect on deep infections.
The permeability of salicylic acid antibacterial solution is nonlinearly positively correlated with its bactericidal efficiency, and it needs to be precisely regulated according to the type of infection. By optimizing the dosage form, adjusting the pH value and combining penetration-enhancing technology, the concentration of the drug in the target tissue can be maximized while ensuring the safety of the drug. Future research should focus on the development of intelligent responsive delivery systems, such as pH-sensitive liposomes, photothermal-triggered release carriers, etc., to achieve site-specific drug penetration and release, and further improve the clinical efficacy of salicylic acid antibacterial drugs.
