Table 1: Results from the assessment of the safety and effectiveness of AMP-containing formulations against oral diseases in clinical trials (published results from the last 5 years). the clinical utility of AMP-containing pharmaceutics. Clinical trials of some other AMP-containing pharmaceutics designed to improve the prevention and treatment of periodontal disease and dental caries are also listed in Table 1.  
To improve the therapeutic utility of AMPs in periodontal disease treatment, [PERSON] et al. constructed two enzyme-activatable prodrugs by combining P-113 AMP (i.e., the 12-amino-acid derivative of Histatin-5) with a charge-shielding toxicity-quencher and a recognition sequence for SAP9 (secreted aspartyl proteases) or RgpB (gingipains) for efficient detection and targeting of _C. albicans_ and _P. gingipalis_, respectively [101]. By offering the targeted release, the prodrug peptides demonstrated high antimicrobial effects toward the microorganisms expressing the trigger protease without considerable toxicity when targets were absent [101]. Histatin-5 was also used as a base for the production of mucoadhesive gel for the treatment of oral mucositis [77]. Research performed both in vitro and in vivo confirmed that a Hist-5/Carbopol 934/hydroxypropyl methylcellulose-containing formulation gave a sustained release profile of Hist-5, antimicrobial activity against _S. aureus_, _P. aeruginosa_, _E. coli_, and _C. albicans_, as well as wound healing-promoting capabilities, justifying further development and utilization of such formulations [77]. Significant progress was also achieved in the development of enhanced biomaterials incorporating AMPs. Most recently, [PERSON] et al. presented a new AMP-containing scaffold showing the potential for treating bone abnormalities, particularly in the craniofacial region. As such, GL13K (i.e., AMP derived from protein saliva) was incorporated into a collagen membrane by self-assembly to create a new bone regeneration scaffold to reduce post-surgical infections and aid in bone regeneration in dental and orthopedic applications. The authors confirmed that a synthetic, self-assembling nanofibrillar membrane displayed both antimicrobial activities and enhanced bone formation in vivo, expanding the knowledge on the utility of AMPs for the fabrication of improved, dual-action oral biomaterials [102]. In another study, [PERSON] et al. aimed to improve the effects and characteristics of microcin C7 (McC7) for use in the treatment of periodontitis. McC7 [78] is an aspartyl tRNA synthetase \"Trojan horse\" inhibitor [103] and is characterized by low protease resistance and susceptibility to unique oral environments such as mastication, salivary flow, and tongue movement. An injectable temperature-sensitive sustained-release hydrogel was proposed as the base for a drug delivery system of this material. Results demonstrated the slow and continuous release of McC7 with simultaneous good biocompatibility and biodegradability accompanied further by antibacterial and anti-inflammatory effects in a periodontitis rat model, which indicated the validity of using such systems in dental diseases. Achievements of nanotechnology have also been utilized for the fabrication of next-generation antibacterial materials and formulations. Polymeric nanopolymers have recently gained attention for use in the treatment of chronic oral inflammatory diseases of bacterial origin, periodontitis in particular [104]. Using another approach, to improve the therapy against multispecies biofilms related to periodontitis, [PERSON] et al. proposed conjugating blue light-activated chlorin-e6 (Ce6) with LL-37 in the form of a nanoemulsion for photodynamic eradication of oral pathogens. The combination of a photosensitizer (PS) with an AMP which permeabilizes bacterial membranes and, thus, permits the penetration of PS and its subsequent intracellular effects was demonstrated as highly efficient.