Table 2.

Summary on Nanoparticulate Delivery Systems for Periodontal Tissue Regeneration.

Nano-DDSs	Characteristic	Clinical Application	Research Findings	Reference
Liposomes	Structural versatility, biocompatibility, biodegradability, non-toxic and nonimmunogenicity	Bubble liposomes plus ultrasound	Providing an efficient technique for delivering plasmid DNA into the gingiva.	Sugano et al. [48,49]
		Negatively charged liposomes	A versatile tool in the field of drug-carrier systems due to their size and hydrophobic and hydrophilic character	Bozzuto et al. [50]
		Liposomes modified with viral fusion proteins	Exhibiting capabilities to fuse with or to disrupt endosomal and/or lysosomal membranes and introduce encapsulated antigenic into cell cytosol.	Kunisawa et al. [51]
		A novel pH-activated nanoparticle comprising a quaternary ammonium chitosan, i.e., N,N,N-trimethyl chitosan, a liposome, and doxycycline (TMC-Lip-DOX NPs)	Achieving superb inhibition of free mixed bacteria and biofilm formation, and showing excellent biocompatibility with human periodontal ligament fibroblasts	Hu et al. [52]
		Minocycline hydrochloride liposomes	Showing significantly stronger and longer inhibition of TNF-α secretion in macrophages compared to periocline and minocycline hydrochloride solution	Liu et al. [54]
		A therapeutic resveratrol-loaded liposomal system (Lipo-RSV)	A potential therapeutic system for the antibiotic-free treatment for periodontal diseases	Shi et al. [55]
		Stealth, long circulating or PEGylated liposomes	Increasing repulsive forces between liposomes and serum-components, reducing immunogenicity and macrophage uptake, enhancing the blood circulation half-life, and reducing the toxicity of encapsulated compound	Di et al. [57]
Polymeric Nanoparticles	Non-immunogenicity, biological inactivity, and the facility of functional groups for covalent coupling of drugs or target moieties	Chitosan (CHT)	An excipient for producing nanoparticles for the treatment of periodontal defects	Ul et al. [59]
		a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs)	Serving as a temporary guided tissue regeneration membrane in periodontal regeneration with the possibility to induce bone regeneration	Mota et al. [66]
		Chitosan/plasmid nanoparticles encapsulating platelet-derived growth factor (PDGF)	Offering a 3D carrier for increased proliferation of periodontal ligament cells	Peng et al. [67]
		Nanogels	Serving as suitable carriers for the delivery of a variety of chemotherapeutics, antisense nucleotides, siRNAs, and peptides	Hajebi et al. [68]
		Cholesterol-bearing pullulan (CHP)-nanogel	Working as a suitable carrier for the W9-peptide, preventing aggregation and increasing the stability of the W9-peptide	Alles et al. [73]
		Asymmetric barrier membranes based on polysaccharide micro-nanocomposite hydrogel	Showing better biocompatibility and higher mechanical properties, indicating its potential for periodontal tissue engineering	He et al. [74]
		Poly (lactic-co-glycolic acid) (PLGA)	Serving as a reference polymer in manufacturing of nanoparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules	Ortega-Oller et al. [75]
		A mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles	Having no cytotoxicity and contributed to cell mineralization	Xue et al. [76]
		Polytetrafluoroethylene (PTFE)	Being commonly used because of its porous microstructure that allows connective tissue in growth	Kameda et al. [77]
		Expanded polytetrafluoroethylene (e-PTFE)	Serving as a membrane barrier for regeneration procedures	Soldatos et al. [78]
		High-density polytetrafluoroethylene membranes (n-PTFE)	Being non-porous, dense, non-expanded and non-permeable	Carbonell et al. [79]
		Polycaprolactone (PCL)	Being capable of mimicking the extracellular matrix (ECM), combining both core-shell and nano-reservoirs functionalization	Bassi et al. [81]
		BMP-2 or BMP-2/Ibuprofen functionalized PCL membranes	Passive release of ibuprofen will decrease the inflammation leading to increased BMP-2 secretion by macrophages while active loading of BMP-2 or other growth factor will directly promote the regeneration of targeted tissue such as alveolar bone	Park et al. [83]
		Chorion membrane (CM) and amnion/chorion membrane (ACM)	Exerting the anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects	Gulameabasse et al. [84]
Inorganic Nanoparticles and Nanocrystals	Chemical stability, thermal resistance, and long-lasting action	Strontium (Sr2+)/strontium ranelate	A cation that stimulates the differentiation of mesenchymal stem cells to develop into bone tissue by suppressing the activity of osteoclasts as bone resorption cells	Pilmane et al. [87]
		Mesoporous bioglass	Favoring the osseointegration with host tissues while inhibiting bacterial activity for better periodontal regeneration	Sriranganathan et al. [92]
		Silver and zinc-based nanoparticle	Exerting significant effects on inhibiting bacterial growth and promoting osteogenic properties	Gaviria et al. [95] & Yoo et al. [96]
		Magnesium oxide nanoparticle	Presenting superior antibacterial activity and osteoinductivity	Liu et al. [97] & Bilal et al. [98]
		Zinc or calcium loaded PolymP-nActive polymeric nanoparticles	Promoting precipitation of calcium phosphate deposits	Osorio et al. [100]
Dendrimers	Hyperbranched structures, multivalent and modifiable surface, interior hydrophilic or hydrophobic shells	Polyamidoamine (PAMAM)	Enhancing aqueous solubility, stability, dissolution, drug release, targeting and pharmacokinetics of various drugs	Chauhan et al. [101]
		PAMAM dendrimers solubilizing triclosan (TCN)	Failing to maintain the previous observations of increased solubility of TCN at lower pH	Gardiner et al. [104]
		PAMAM dendrimers and silica based nitric oxide (NO) release	Displaying considerably less toxicity for human gingival fibroblasts at the levels required to kill periodontal pathogens	Backlund et al. [106]