Abstract
Background: Periodontal disease is an immuno-inflammatory condition of tissues that surround and hold the teeth. It is the disease which succeeds in all races, groups and both genders. Almost 10 to15% of the global population gets suffered from severe periodontitis as per WHO reports. Periodontal disease may likely cause other systemic diseases such as cardiovascular disease and pre-term low birth weight infants. Mechanical removal of plaques and calculus deposits from supra and subgingival environment is the backbone of periodontal treatment till date whereas complete elimination of these deleterious agents is quite unrealistic as the pocket depth increases.
Recent Approaches: Recently controlled local drug delivery application is more encouraging in comparison to systemic approach as it mainly targets to enhance the therapeutic efficacy by maintaining site-specificity, avoiding first pass metabolism, reduction in gastrointestinal (GI) side effects and decreasing the dose. Several drugs such as antiseptics and antibiotics alongwith various carriers are being formulated as local drug delivery systems for effective management of the disease. Various local delivery systems reported are fibers, films, strips, compacts, injectables, microparticles, vesicular carriers, gels and nanoparticles. These local carriers provide effective prolonged treatment at the site of infection at reduced doses. This review enlightens detailed pathophysiology and various phases of periodontitis, challenges in treatment of disease and various antimicrobial agents (along with their marketed formulations) used. The main emphasis of the review is to cover all carrier systems developed so far for local delivery application in the effective management of periodontitis, as a patient compliant drug therapy.
Keywords: Antimicrobial, controlled, gels, fibers, local drug delivery, periodontitis.
Graphical Abstract
[1]
Pérez-Chaparro PJ, Gonçalves C, Figueiredo LC, et al. Newly Identified
Pathogens Associated with Periodontitis: A Systematic
Review. J Dent Res 2014; 93(9): 846-58.
[2]
Kaplish V, Walia MK, Hari Kumar SL. Local drug delivery systems in the treatment of periodontitis: a review. Pharmacophore (An International Research Journal) 2013; 4(2): 39-49.
[3]
Arunachalam R, Rajeev V, Vedam V, Ganapathy S, Dhanavel J. Perioceutics in the management of Periodontal Disease. J Young Pharm 2017; 9(1)
[4]
Jain N, Jain GK, Javed S, et al. Recent approaches for the treatment of periodontitis. Drug Discov Today 2008; 13(21-22): 932-43.
[5]
Joshi D, Garg T, Goyal AK, Rath G. Advanced drug delivery approaches against periodontitis. Drug Deliv 2016; 23(2): 363-77.
[6]
Mathew MM, Joseph J, Vineetha VC. Periodontitis-Disease and Treatment - A Review. Int J Pharm Chem Sci 2014; 3(3): 791-800.
[8]
Jacob S. Global Prevalence of Periodontitis: A Literarure Review. Periodontol 2016; 3(1): 26-30.
[9]
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases www.theLancet.com2005; 366(9499): 1809-20.
[10]
Lang NP, Adler R, Joss A, Nyman S. Absence of bleeding on probing. An indicator of periodontal stability. J Clin Periodontol 1990; 17(10): 714-21.
[11]
Lang NP, Joss A, Orsanic T, Gusberti FA, Siegrist BE. Bleeding on probing. A predictor for the progression of periodontal disease? J Clin Periodontol 1986; 13: 590-6.
[12]
Joss A, Adler R, Lang NP. Bleeding on probing. A parameter for monitoring periodontal conditions in clinical practice. J Clin Periodontol 1994; 21: 402-8.
[13]
Haffajee AD, Socransky SS, Lindhe J, Kent RL, Okamoto H, Yoneyama T. Clinical risk indicators for periodontal attachment loss. J Clin Periodontol 1991; 18: 17-25.
[14]
Van der Velden U, Abbas F, Winkel EG. Probing considerations in relation to susceptibility to periodontal breakdown. J Clin Periodontol 1986; 13: 894-9.
[15]
Van der Velden U, Abbas F, Hart AA. Experimental gingivitis in relation to susceptibility to periodontal disease. (I) Clinical observations. J Clin Periodontol 1985; 12: 61-8.
[18]
Armitage GC. Development of a Classification System for Periodontal Diseases and Conditions. Ann Periodontol 1999; 4(1): 1-6.
[19]
Highfield J. Diagnosis and classification of periodontal disease. Aust Dent J 2009; 54(1)(Suppl.): S11-26.
[20]
Lindhe J, Westfelt E, Nyman S, Socransky S, Hafajee AD. Long-term effect of surgical/nonsurgical treatment of periodontal disease. J Clin Periodontol 2005; 11(7): 448-58.
[21]
Hill RW, Ramfjord SP, Morrison EC. Four types of periodontal treatment compared over two years. J Periodontol 1981; 52: 655-62.
[22]
Isidor F, Karring T. Long-term effect of surgical and non-surgical periodontal treatment. A 5-year clinical study. J Periodontal Res 1986; 21: 462-72.
[23]
Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP, Dyer JK. Longterm evaluation of periodontal therapy: I. Response to 4 therapeutic modalities. J Periodontol 1996; 67: 93-102.
[24]
Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP, Dyer JK. Longterm evaluation of periodontal therapy: II. Incidence of sites breaking down. J Periodontol 1996; 67: 103-8.
[25]
Garg S. Local Drug Delivery Systems as an Adjunct to Cure Periodontitis. The Novel Dental Applicant. Pharm Methods 2015; 6(1)
[26]
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. Int J Drug Deliv 2009; 1: 1-14.
[27]
Maurizio S. Tonetti. The topical use of antibiotics in periodontal pockets. in: N.P. Lang, T. Karring, J. Lindhe (Eds.),. Proceedings of the Second European Workshop on Periodontology, Quintessence. London. 1997; pp. 109-32.
[28]
Garrett S, Johnson L, Drisko CH, et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. J Periodontol 1999; 70(5): 490-503.
[29]
Slots J, Rams TE. Antibiotics in periodontal therapy: advantages and disadvantages. J Clin Periodontol 1990; 17: 479-93.
[30]
Van Steenebergh D, Bercy P, Kohl J. Subgingival Minocycline Hydrochloride ointment in moderate to severe chronic adult periodontitis a randomised double blind, vehicle controlled multicenter study. J Periodontol 1993; 64: 637-44.
[31]
Kornman KS. Controlled release local delivery-Antimicrobials in periodontics. Prospects for the future. J Periodontol 1993; 64: 782-91.
[32]
De Graaff J, Van Winkelhoff AJ, Goen RJ. The role of Actinobacillus actinomycetemcomitans in periodontal disease. Infection 1989; 17: 269-71.
[34]
Kameswari K, Ambalavanan NT, Ramakrishna T, Saravana KR. Effectiveness of a controlled release chlorhexidine chip (PerioCol™-CG) as an adjunctive to scaling and root planning when compared to scaling and root planing alone in the treatment of chronic periodontitis: A comparative study. J Indian Soc Periodontol 2012; 16(4): 553-7.
[35]
Maurstad G, Stokke BT. Metastable and stable states of xanthan polyelectrolyte complexes studies by atomic force microscopy. Biopolymers 2004; 74: 199-213.
[36]
Andreopoulos AG, Tarantili PA. Xanthan gum as a carrier for controlled release of drugs. J Biomater Appl 2001; 16: 34-46.
[37]
Agarwal E, Pradeep AR, Bajaj P, Naik SB. Efficacy of local drug delivery of 0.5% clarithromycin gel as an adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a randomized controlled clinical trial. J Periodontol 2012; 83(9): 1155-63.
[38]
Schwach-Abdellaouia K. VivienCastionib N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm 2000; 50: 8399.
[40]
Goodson J, Haffajee A, Socransky S. Periodontal therapy by local delivery of tetracycline. J Clin Periodontol 1979; 6: 83-92.
[41]
Goodson JM. Monolithic tetracycline containing fibers for controlled delivery to periodontal pockets. J Periodontol 1983; (54): 575-9.
[42]
Garg T, Rath G, Goyal AK. Comprehensive review on additives of topical dosage forms for drug delivery. Drug Deliv 2014.
[43]
Vandekerckhove BN, Quirynen M, Van Steenberghe D. The use of tetracycline-containing controlled-release fibers in the treatment of refractory periodontitis. J Periodontol 1997; 68: 353-61.
[44]
Anderson H. Treatment of chronic periodontitis: a site-specific fiber placement technique. Pract Periodontics Aesthet Dent 1996; 8(6): 565-70.
[45]
Goodson JM, Cugini MA, Kent RL, et al. Multicenter evaluation of tetracycline fiber therapy: II. Clinical response. J Periodontal Res 1991; 26(4): 371-9.
[46]
Johnston D, Choonara YE, Kumar P, du Toit LC, van Vuuren S, Pillay V. Prolonged delivery of ciprofloxacin and diclofenac sodium from a polymeric fibre device for the treatment of peridontal disease. Biomed Res Int 2013.Article ID 460936
[47]
Sachdeva S, Agarwal V. Evaluation of commercially available biodegradable tetracycline fiber therapy in chronic periodontitis. J Indian Soc Periodontol 2011; 15: 130-4.
[48]
Chang HI, Lau YC, Yan C, Coombes AG. Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers. J Biomed Materials Res part A 2008; 84: 230-7.
[49]
Tonetti M, Cugini M, Goodson J. Zero-order delivery with periodontal placement of tetracycline-loaded ethylene vinyl acetate fibers. J Periodontal Res 1990; 25: 243-9.
[50]
Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm 2000; 50: 83-99.
[51]
Leung WK, Jin L, Yau JY, Sun Q, Corbet EF. Microflora cultivable from minocycline strips placed in persisting periodontal pockets. Arch Oral Biol 2005; 50: 39-48.
[52]
Friesen LR, Williams KB, Krause LS, Killoy WJ. Controlled local delivery of tetracycline with polymer strips in the treatment of periodontitis. J Periodontol 2002; 73: 13-9.
[53]
Ozcan G, Taner I, Doganay T, et al. Use of membranes containing 20% chlorhexidine and 40% doxycycline for treatment of chronic periodontal pockets. J Nihon Univ Sch Dent 1994; 36: 191-8.
[54]
Moran J, Addy M, Wade W, Newcombe R. The use of antimicrobial acrylic strips in the non-surgical management of chronic periodontitis. Clin Mater 1990; 6: 123-35.
[55]
Deasy P, Collins AE, Maccarthy DJ, Russell R. Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. J Pharm Pharmacol 1989; 41: 694-9.
[56]
Vyas SP, Sihorkar V, Mishra V. Controlled and targeted drug delivery strategies towards Intraperiodontal pocket disease. J Clin Pharm Ther 2000; 25(1): 21-42.
[57]
Jeffcoat M, Bray KS, Cianico SG, et al. Adjunctive use of a sub gingival controlled-release Chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planning alone. J Periodontol 1998; 69(9): 989-97.
[58]
Azmak N, Atilla G, Luoto H, Sorsa T. The effect of sub gingival controlled- release delivery of chlorhexidine chip on clinical parameters and matrix metalloproteinase-8 levels in gingival crevicular fluid. J Periodontol 2002; 73(6): 608-15.
[59]
Grover V, Kapoor A, Malhotra M, Battu VS, Bhatia A, Sachdeva S. To assess the effectiveness of a chlorhexidine chip in the treatment of chronic periodontitis: A clinical and radiographic study. J Indian Soc Periodontol 2011; 15(2): 139-46.
[60]
Kondreddy K, Ambalavanan N, Ramakrishna T, Kumar RS. Effectiveness of a controlled release chlorhexidine chip (PerioColTM-CG) as an adjunctive to scaling and root planning when compared to scaling and root planning alone in the treatment of chronic periodontitis: A comparative study. J Indian Soc Periodontol 2012; 16(4): 553-7.
[61]
Labib GS, Aldawsari HM, Badr-Eldin SM. Metronidazole and pentoxifylline films for the local treatment of chronic periodontal pockets: preparation, in vitro evaluation and clinical assessment. Expert Opin Drug Deliv 2014; 11: 855-65.
[62]
El-Kamel AH, Ashri LY, Alsarra IA. Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases. AAPS PharmSciTech 2007; 8: 184-94.
[63]
Cetin EO, Buduneli N, Atlıhan E, Kırılmaz L. In vitro studies of a degradable device for controlled-release of meloxicam. J Clin Periodontol 2005; 32: 773-7.
[64]
Minabe M, Takeuchi K, Nishimura T, Hori T, Umemoto T. Therapeutic effects of combined treatment using tetracycline-immobilized collagen film and root planning in periodontal furcation pockets. J Clin Periodontol 1991; 18(5): 287-90.
[65]
Kyun K, Yun K, Young J, Pyoung CC, Heui SS. Development of minocycline containing polycaprolactone film as a local drug delivery. Taehan Chikkwa Uisa Hyophoe Chi 1990; 28(3): 279-90.
[66]
Golomb G, Friedman M, Soskolne A, Stabholz A, Sela MN. Sustained release device containing metronidazole for periodontal use. J Dent Res 1984; 63: 1149-53.
[67]
Jones SD, Woolfson DA, Brown FA, Michael J, Neill O. Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to periodontal pocket. In vitro release kinetics, syringeability, mechanical and mucoadhesive properties. J Control Release 2002; 49(1): 71-9.
[68]
Garg T. Current nanotechnological approaches for an effective delivery of bio-active drug molecules in the treatment of acne. Artif Cells Nanomed Biotechnol 2014; 1-8.
[69]
Garg T, Goyal AK. Medicated chewing gum: patient compliance oral drug delivery system. Drug Deliv Lett 2014; 4: 72-8.
[70]
Esposito E, Carrota V, Scabbia A, Trombelli L, Antena PD, Menegatti E. Comparative analysis of tetracycline containing dental gels: poloxamer and monoglyceride based formulations. Int J Pharm 1996; 142(1): 9-23.
[71]
Arora N, Singh K, Garg T. Areas of nanomedicine applications. Int J Life Sci Biotechnol Pharma Res 2012; 2: 216-27.
[72]
Zhao Y, Kang J, Tan T. Salt, pH and temperature-responsive semi-interpenetrating polymer network hydrogel based on poly (aspartic acid) and poly (acrylic acid). Polymer 2006; 47: 7702-10.
[73]
Garg T, Singh S, Goyal AK. Stimuli-sensitive hydrogels: an excellent carrier for drug and cell delivery. Crit Rev Ther Drug Carrier Syst 2013; 30: 369-409.
[74]
Wennstrom JL, Thomasi C. Locally delivered doxycycline improve the healing following non-surgical periodontal therapy in smokers. J Clin Periodontol 2004; 31(8): 589-95.
[75]
Javali MA, Vandana KL. A comparative evaluation of atrigel delivery system (10% doxycycline hyclate) Atridox with scaling and root planning and combination therapy in treatment of periodontitis: A clinical study. J Indian Soc Periodontol 2012; 16(1): 43-8.
[76]
Van Steenebergh D, Bercy P, Kohl J. Sub gingival Minocycline Hydrochloride ointment in moderate to severe chronic adult periodontitis a randomised double blind, vehicle controlled multicenter study. J Periodontol 1993; 64(7): 637-44.
[77]
Rao NS, Pradeep AR, Bajaj P, Kumari M, Naik SB. Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial. Aust Dent J 2013; 58: 156-62.
[78]
Dabhi MR, Sheth NR. Formulation development of physiological environment responsive periodontal drug delivery system for local delviery of metronidazole benzoate. Drug Dev Ind Pharm 2013; 39: 425-36.
[79]
Agarwal E, Pradeep A, Bajaj P, Naik SB. Efficacy of local drug delivery of 0.5% clarithromycin gel as an adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a randomized controlled clinical trial. J Periodontol 2012; 83: 1155-63.
[80]
Flemmig TF, Petersilka G, Volp A, et al. Efficacy and safety of adjunctive local moxifloxacin delivery in the treatment of periodontitis. J Periodontol 2011; 82: 96-105.
[81]
Gupta R, Pandit N, Aggarwal S, Verma A. Comparative evaluation of subgingivally delivered 10% doxycycline hyclate and xanthan-based chlorhexidine gels in the treatment of chronic periodontitis. J Contemp Dent Pract 2008; 9: 25-32.
[82]
Akıncıbay H. ¸Senel S, Yetkin Ay, Z. Application of chitosan gel in the treatment of chronic periodontitis. J Biomed Mater Res Part B: Appl Biomater 2007; 80: 290-6.
[83]
Maheshwari M, Miglani G, Mali A, Paradkar A, Yamamura S, Kadam S. Development of tetracycline-serratiopeptidase-containing periodontal gel: formulation and preliminary clinical study. AAPS PharmSciTech 2006; 7(3): 62-71.
[84]
Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. J Periodontol 2001; 72(11): 1535-44.
[85]
Jhimger N, Kapoor D, Jain R. Comparison of Periochip (chlorhexidine gluconate 2.5 mg) and Arestin (Minocycline hydrochloride 1 mg) in the management of chronic periodontitis. Indian J Dent 2015; 6(1): 20-6.
[86]
Collins AE, Desay PB, MacCarthy DJ, Shanely DB. Evaluation of controlled release compact containing tetracycline hydrochloride bonded to tooth for the treatment of periodontal diseases. Int J Pharm 1989; 51(2): 103-14.
[87]
Baker RW. A controlled release drug delivery system for periodontal pocket. Proceeding International Symposium on
Control Release Bioact Mater. 1988; 238a-b.
[88]
Pichayakorn W, Boonme P. Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment. Mater Sci Eng C Mater Biol 2013; 33: 1197-202.
[89]
De Sousa FO, Blanco-Mendez J, Perez-Estevez A, Seoane Prado R, Luzardo Alvarez A. Effect of zein on biodegradable inserts for the delivery of tetracycline within periodontal pockets. J Biomater Appl 2012; 27(2): 187-200.
[90]
Rao SK, Setty S, Acharya AB, Thakur SL. Efficacy of locally delivered doxycycline microspheres in chronic localized periodontitis and on Porphyromonas gingivalis. J Investig Clin Dent 2012; 3: 128-34.
[91]
Zingale J, Harpenau L, Bruce G, Chambers D, Lundergan W. The effectiveness of scaling and root planing with adjunctive time-release minocycline using an open and closed approach for the treatment of periodontitis. Gen Dent 2011; 60(4): 300-5.
[92]
Garg T, Singh O, Arora S, Murthy R. Patented microencapsulation techniques and its application. J Pharm Res 2011; 4: 2097-102.
[93]
Kong LX, Peng Z, Li SD, Bartold PM. Nanotechnology and its role in the management of periodontal diseases. Periodontol 2000 2006; 40: 184-96.
[94]
Lu Z, Rong K, Li J, Yang H, Chen R. Size-dependent antibacterial activities of silver nanoparticles against oral anaerobic pathogenic bacteria. J Mater Sci Mater Med 2013; 24: 1465-71.
[95]
Wayakanon K, Thornhill MH, Douglas CW, et al. Polymersome-mediated intracellular delivery of antibiotics to treat Porphyromonas gingivalis-infected oral epithelial cells. FASEB J 2013; 27: 4455-65.
[96]
Sindhura Reddy N, Sowmya S, Bumgardner JD, Chennazhi KP, Biswas R, Jayakumar R. Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management. Biochim Biophys Acta 2014; 1840: 2080-90.
[97]
Bako J, Szepesi M, Marton I, Borbrly J, Hegedus C. Synthesis of nanoparticles for dental drug delivery systems. Fogorvosi Szemle 2007; 100: 109-13.
[98]
Moulari B, Lboutounne H, Chaumont JP, Guilaume Y, Millet J, Pellequer Y. Potentiation of the bactericidal activity of Harungana madagascariensis Lam. ex Poir. (Hypericaceae) leaf extract against oral bacteria using poly (D, LLactide-Co-Glycolide) nanoparticles: in vitro study. Acta Odontol Scand 2006; 64: 153-8.
[99]
Garg T, Goyal AK. Liposomes: targeted and controlled delivery system. Drug Deliv Lett 2014; 4: 62-71.
[100]
Di Turi G, Riggio C, Vittorio O. Sub-micrometric liposomes as drug delivery systems in the treatment of periodontitis. Int J Immunopathol Pharmacol 2011; 25: 657-70.
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