## 5 Nanoformulations for Wound Healing
### Nanoparticles Loaded with Phytochemicals
#### 5.2.3 Other Nanoformulations Loaded with Phytochemicals and Extracts  
Skin injuries and resulting wounds pose significant clinical challenges, prompting the continuous exploration of advanced therapeutic approaches to promote tissue regeneration. Among promising solutions, tissue engineering, particularly using polymeric scaffolds such as hydrogels, has gained considerable attention. CS and ALG are frequently utilized in hydrogel preparation for wound healing applications given their favorable biocompatibility, biodegradability, and supportive properties. Incorporating natural bioactive compounds, including essential oils and nettle (_Urtica dioica_) extracts, into these hydrogel scaffolds can significantly enhance wound repair processes. Employing nanocarriers such as nanoemulsions to encapsulate nettle extract and essential oils further improves their stability and bioavailability within the hydrogel matrix, thereby promoting more effective wound healing outcomes. In one study, nanoemulsions loaded with nettle extract and oil were successfully integrated into chitosan-alginate hydrogels, generating promising nanocomposite dressings. The developed nanocomposites demonstrated potent antibacterial activity, minimal cytotoxic effects, enhanced cell adhesion, a superior water absorption capacity, and an excellent hemocompatibility, highlighting their substantial potential as advanced dressing materials for effective wound healing [111]. _Perovskia abrotanoides_ (P:a) karel is a medicinal plant known traditionally for its antimicrobial, anti-inflammatory, and antioxidant effects in wound treatment. Incorporating nanoemulsions (NEs) into chitosan gels has been demonstrated to enhance drug bioavailability, stability, skin penetration, and wound healing efficacy. One study evaluated the wound healing potential of a P.a essential oil nanoemulsion embedded in chitosan gel on full-thickness circular skin wounds in Wistar rats. The nanoemulsion was prepared using essential oil extracted from the flowering branches of Perovskia abrotanoides through ultrasonic emulsification and subsequently integrated into a 2% chitosan hydrogel, forming a P.a-NE-loaded chitosan gel. The optimized formulation was characterized by its particle size, stability, viscosity, and antimicrobial activity. Its in vivo wound healing effectiveness was assessed on days 3, 7, 14, and 21 post-application in Wistar rats. Histopathological analyses, including hematoxylin-eosin (HE) and [PERSON]'s trichrome staining, were performed to evaluate tissue regeneration and collagen deposition within the wound area. The optimized P.a NE formulation demonstrated an average particle size of 13 \(\pm\) 0.5 nm, a zeta potential of \(2.9\pm 0.95\) mV, and quasi-spherical morphology confirmed by transmission electron microscopy (TEM), exhibiting promising characteristics for clinical wound healing applications [112]. Lupeol, a pentacyclic triterpene, exhibits notable wound healing properties; nonetheless, its low water solubility limits its clinical use. To address this challenge, lupeol was encapsulated in silver-modified chitosan nanoparticles and subsequently incorporated into a thermosensitive, self-assembling sericin hydrogel. The results demonstrated that the lupeol encapsulation into the nanoparticles reached 62.1%, while exhibiting potent an tibacterial properties against both Gram-positive and Gram-negative pathogens, alongside minimal hemolytic activity (<5%). The application of the CS-Ag-L-NPs sericin hydrogel to infected wounds markedly inhibited bacterial growth, accelerated re-epithelialization, mitigated inflammation, and improved collagen deposition, collectively enhancing overall wound healing outcomes. These findings suggest that the CS-Ag-L-NPs-loaded sericin hydrogel possesses substantial therapeutic potential for simultaneously enhanced wound repair and the effective control of microbial infections in wound management scenarios [113]. Table 2 shows various applications of phytochemical-loaded nanocarriers.