## 5 Nanoformulations for Wound Healing
### Nanoparticles Loaded with Phytochemicals
#### 5.2.1 Inorganic Nanocarriers  
_P. aeruginosa_ is the predominant pathogen associated with burn wound infections, leading to slower wound healing and the possible development of chronic wounds. Consequently, developing effective antimicrobial therapies that simultaneously accelerate wound recovery has become essential. In this context, a novel nanosystem was examined, using mesoporous silica-coated UCNPs (UCNPmSiO\({}_{2}\)) as a drug delivery vehicle for curcumin and ceftazidime (CAZ). An F23 aptamer was used to create a dual-targeting functional cell membrane from pre-treated macrophage membranes (pM). The nanosystem exhibited a spherical morphology with a consistent particle shape and displayed a negative zeta potential. In vitro studies revealed the superior antibacterial activity of the nanosystem compared to traditional antibiotic treatments alone. Furthermore, the nanosystem was able to effectively inhibit and eradicate bacterial biofilms, achieving enhanced antibacterial selectivity and activity. Importantly, near-infrared light irradiation augmented these antibacterial and anti-biofilm properties via a photodynamic mechanism. In the mouse model of _P. aeruginosa_-infected skin wounds, the nanosystem successfully eliminated bacterial infections and notably promoted wound healing, without evident systemic toxicity. Thus, this study represents a promising and innovative targeted nanotherapeutic approach, particularly suitable for managing Pseudomonas aeruginosa-related skin wound infections [103]. Another study investigated the therapeutic efficacy of a hydrogel containing zinc oxide nanoparticles synthesized from _Gliricidia spinum_ (Jacq. )-GSL Kunth. ex. Walp. leaf extract in diabetic wound management. The chromatographic analysis of the leaf ethanolic extract identified the following major bioactive constituents: apigenin-7-O-glucose, kaempferol, and protocatechuric acid, all recognized for their anti-inflammatory effects. The prepared hydrogel incorporated both GSL ethanolic extract and zinc oxide nanoparticles, demonstrating controlled-release characteristics along with an optimal swelling capacity. In diabetic wound models, the nanoformulations significantly accelerated tissue repair, minimized cellular apoptosis, and effectively modulated inflammatory responses. These outcomes were supported by evaluations of wound morphology, healing progression, histopathological examinations, and immunohistochemical staining. Collectively, these results underscore  
Figure 7: Common nanocarriers loaded with phytochemicals Inorganic silver, gold, zinc oxide, and polymeric nanoparticles based on chitosan, zein, and alginate. the promising potential of the nanoproduct as an effective therapeutic agent for diabetic wound healing [104]. These findings were further validated by evaluating specific biomarkers involved in wound healing. Treatment resulted in a marked decrease in the levels of vascular cell adhesion molecule-1 and advanced glycation end-products (AGES), both known to negatively impact wound repair. Simultaneously, there was a significant elevation in beneficial mediators, including the anti-inflammatory cytokine interleukin-10 (IL-10) and platelet-derived growth factor (PDGF), both critical for promoting tissue regeneration and angiogenesis. Overall, the evidence presented underscores the promising therapeutic potential of Gliricidia sepium-derived zinc oxide nanoparticles hydrogel (GSL ZnONPs HG) as an effective intervention to enhance diabetic wound healing through the modulation of inflammation and the stimulation of reparative growth factors [104]. Current wound dressings often demonstrate limitations such as rigidity, an insufficient mechanical integrity, a low porosity, adherence to wound surfaces, and a lack of antimicrobial properties, thereby restricting their clinical efficacy. To address these challenges, a microporous, antibacterial chitosan-sericin-nano zinc oxide (CS-SS-nZnO) nanocomposite was developed to provide an effective microbial barrier and enhance wound healing.