Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro characterization and antimicrobial study

Abstract

Background: This study aimed to formulate and characterize in-situ gel containing levofloxacin and metronidazole to release drugs in controlled manner for treatment of periodontitis.

Material and methods: Medicated in-situ gel with levofloxacin (10% w/v), metronidazole (25% w/v) and vehicle in-situ gel without drugs having poloxamer 407 (20% w/v) and chitosan (0.5%, 1%, 1.5%, 2.0% 2.5% w/v) were prepared and characterized for physicochemical, mechanical properties, stability and in-vitro drug release. Fourier transform infrared spectroscopy and differential scanning calorimetery studies were done. Optimized formulation was evaluated by scanning electron microscope (SEM) and in-vitro antimicrobial activity against 5 bacterial strains.

Results: The results revealed that drugs and polymers were compatible to formulate. All formulations were light yellow, clear and syringeable except formulation having 2.5% w/v chitosan. pH was in the range of 6.20 to 6.74. 1.0% w/v and 1.5% w/v chitosan formulations showed gelation temperature 37 ± 0.32 °C and 34 ± 0.21 °C. Further, mucoadhesive strength indicated mucoadhesivity of gel. In-vitro release study of 1.5% w/v chitosan formulation showed initial burst where about 55-60% MZ and 60-70% LVF got released within 6-7 hrs followed by sustained release upto 48 hrs. SEM images of 1.5% w/v chitosan optimized medicated in-situ and vehicle in-situ gel appeared similar indicating homogeneous mixing of polymers with drugs. In-vitro antimicrobial study showed that medicated in-situ gel was more effective than vehicle.

Conclusions: In conclusion, optimized 1.5% w/v chitosan in-situ gel was thermoresponsive, mucoadhesive, syringeable, and released drugs in slow and controlled manner with effectiveness against broad range of microbes.

Keywords: In-situ gel; Mucoadhesive; Periodontal disease; Poloxamer 407; Thermoresponsive.

Figures

Fig. 1

a) FTIR overlap spectra, b) DSC overlap graph of levofloxacin, metronidazole, poloxamer 407, chitosan, physical mixture of polymers and drugs.

Fig. 2

Graph showing the cumulative percentage release of a) Metronidazole and b). Levofloxacin at predetermined time period from different formulations c) Levofloxacin & metronidazole at predetermined time period from the optimized 1.5%w/v chitosan formulation before storage, after storage at 40 °C and at 5 °C.

Fig. 3

i) Scanning electron microscopic images of liquid vehicle gel (P1, P2, P3) and 1.5%w/v chitosan (S1, S2, S3) at different magnifications 1, 5 and 10 KX, ii) Scanning electron microscopic images of dried 1.5%w/v chitosan in situ gel at different magnifications 2, 5 and 10 KX.

Fig. 4

In-vitro antimicrobial study showing zone of inhibition in different microorganisms a. Klebsiella pneumoniae b. Escheria coli c. Staphyloccocs aureus d. Vibrio cholarie e. Proteus vulgaris.