Wound management remains challenging not only because of infection risk but also because of delayed healing. In practice, clinicians and patients need a topical product that can control pain, avoid irritating tissues, be easy to apply on uneven or sensitive surfaces, and support tissue repair. This is why interest in advanced local delivery systems, including sprayable hydrogels, continues to grow [2, 3].

A study published in Pharmaceutics describes a thermosensitive sprayable hydrogel containing lidocaine and allantoin for wound care [1]. The concept addresses a clear clinical need: reducing application-related pain, minimizing dosing variability, achieving more uniform surface coverage, and combining symptomatic relief with support for tissue regeneration.

What the technology is about

The system is a spray-gel based on poloxamer 407 and chitosan. Poloxamer 407 provides thermosensitive behavior: the formulation remains fluid at low temperatures and transitions into a gel at skin temperature. Chitosan is included to enhance bioadhesion and improve retention on the wound surface. The formulation contains two active ingredients: lidocaine hydrochloride (5%) for rapid local analgesia and allantoin (0.5%) associated with tissue repair support and reduced local irritation [3–5].

The formulation appears well-justified. Its liquid state allows for non-contact application, which is particularly relevant for painful or sensitive areas. Subsequent gel formation may improve retention on the wound. Lidocaine is intended to provide rapid pain relief and partially modulate inflammation, while allantoin is considered a component supporting cellular regeneration. Importantly, antibacterial activity was not evaluated in this study; therefore, no conclusions can be drawn regarding infection control.

The authors also highlight that, to their knowledge, no hydrogel system combining lidocaine and allantoin in a thermosensitive spray format has been previously described. This suggests not just a new combination of ingredients but a new delivery approach designed for non-contact, more uniform application.

Results of the preclinical study

The study was conducted at a preclinical laboratory level. Using response surface methodology, the authors optimized concentrations of poloxamer 407 and chitosan to balance three key parameters: viscosity, sprayability, and bioadhesion. Two optimized formulations were selected: S1 and S2.

These formulations were extensively characterized. Parameters included pH, gelation temperature, rheology, spray diameter, bioadhesion, content uniformity, lidocaine release via dialysis, cytotoxicity in HaCaT keratinocytes, cell migration in a scratch assay, and TNF-α expression. In other words, the study attempted to link formulation properties with biological behavior.

From a practical standpoint, the key findings can be summarized as follows.

• Physicochemical properties

Both formulations maintained viscosity suitable for spraying at room temperature (42.7 mPa·s for S2 and 58.7 mPa·s for S1) and demonstrated rapid gelation at temperatures close to skin conditions (28.7±0.6°C for S1 and 29.3±0.3°C for S2)

• Behavior after application

The system is applied as a liquid and then transitions into a gel, which may improve retention; S2, with lower viscosity, showed a wider spray diameter and may be more suitable for larger areas.

• Environmental parameters

The pH of both formulations was approximately 4.35–4.52, within the acidic range considered acceptable for acute wound conditions.

• Drug release

Lidocaine release was rapid, reaching approximately 95–100% by 120 minutes; the more viscous S1 slightly slowed early diffusion.

• Cytotoxicity and biocompatibility

In the MTT assay, keratinocyte viability was 93.89% (S1) and 95.74% (S2); formulations containing only allantoin showed values above 100%, likely reflecting its proliferative effect.

• Cell migration (scratch assay)

The most pronounced wound closure after 24 hours was observed in formulations combining lidocaine and allantoin.

• Anti-inflammatory effect

In an LPS-induced inflammation model, both full formulations significantly reduced TNF-α expression, whereas blank bases showed no such effect.

Taken together, these findings suggest a well-designed platform: the carrier enables application and retention, lidocaine provides rapid analgesia, and allantoin, together with the matrix, may support cellular processes relevant to repair. However, all results are limited to laboratory models.

Limitations and clinical relevance

The main limitation, acknowledged by the authors, is that the study is entirely in vitro. It does not include clinical or even in vivo animal data. Therefore, the findings cannot be directly translated into clinical practice. It remains unclear how the system would perform on real wounds of different types, including moist, exudative, or infected surfaces, or how it would behave during repeated application.

Another limitation is methodological: the authors were unable to reliably quantify allantoin release due to spectral overlap with lidocaine in UV analysis. While lidocaine release was clearly demonstrated, allantoin kinetics require more specific analytical methods. In addition, no clinical safety data are available; safety conclusions are based only on cellular models.

For clinical practice, this means the following. This is not a ready-to-use treatment standard, but a promising delivery platform. It may be particularly relevant for situations where non-contact application, rapid pain relief, and retention on the wound surface are important. However, clinical conclusions are premature. At present, this is a strong pharmaceutical and biomaterials study that sets the direction for further in vivo and clinical research.

Conclusion

The study demonstrates that a thermosensitive spray-gel with lidocaine and allantoin can combine several desirable properties of modern topical systems: non-contact application, rapid gelation, bioadhesion, and fast lidocaine release. At the laboratory level, the system showed good biocompatibility and supported processes associated with keratinocyte recovery. A key strength of the work is the integration of formulation science with biological evaluation. For clinicians, the main takeaway is clear: this is a promising but still preclinical technology worth monitoring, particularly in the context of developing more comfortable topical wound-care solutions.

References

1. Arpa M.D., Biltekin Kaleli S.N. Thermosensitive sprayable lidocaine-allantoin hydrogel: optimization and in vitro evaluation for wound healing. Pharmaceutics 2025; 17(12): 1607.
2. Freedman B.R., Hwang C., Talbot S. et al. Breakthrough treatments for accelerated wound healing. Sci Adv 2023; 9: eade7007.
3. Giuliano E., Gagliardi A., Farhan A. et al. Poloxamer 407-based hydrogels containing rutin enhance in vitro and in vivo wound-healing outcomes. ACS Appl Bio Mater 2025; 8: 1972-1983.
4. Karnina R., Arif S.K., Hatta M., Bukhari A. Molecular mechanisms of lidocaine. Ann Med Surg (Lond) 2021; 69: 102733.
5. Saucedo-Acuna R.A., Meza-Valle K.Z., Cuevas-Gonzalez J.C. et al. Characterization and in vivo assay of allantoin-enriched pectin hydrogel for the treatment of skin wounds. Int J Mol Sci 2023; 24(8): 7377.