Tailored Doxycycline Hyclate Loaded In Situ Gel for the Treatment of Periodontitis: Optimization, In Vitro Characterization, and Antimicrobial Studies

Ranch, Ketan M.; Maulvi, Furqan A.; Koli, Akshay R.; Desai, Ditixa T.; Parikh, Rajesh K.; Shah, Dinesh O.

doi:10.1208/s12249-021-01950-x

Cited by 25 publications

(15 citation statements)

References 60 publications

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“…DH is an antibiotic that has been used for treating periodontitis. The DH-loaded polymer-based drug delivery systems have been formulated to sustain drug release in order to decrease the frequency of administration [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Lime Peel Oil–Incorporated Rosin-Based Antimicrobial In Situ Forming Gel

Khaing

Mahadlek

Okonogi

et al. 2022

Gels

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Localized intra-periodontal pocket drug delivery using an injectable in situ forming gel is an effective periodontitis treatment. The aqueous insoluble property of rosin is suitable for preparing a solvent exchange-induced in situ forming gel. This study aims to investigate the role of incorporating lime peel oil (LO) on the physicochemical properties of injectable in situ forming gels based on rosin loaded with 5% w/w doxycycline hyclate (DH) in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP). Their gel formation, viscosity, injectability, mechanical properties, wettability, drug release, and antimicrobial activities were evaluated. The presence of LO slowed gel formation due to the loose precipitate formation of gel with a high LO content. The viscosity and injectability were slightly increased with higher LO content for the DH-loaded rosin-based in situ forming gel. The addition of 10% LO lowered gel hardness with higher adhesion. LO incorporation promoted a higher drug release pattern than the no oil-added formulation over 10 days and the gel formation rate related to burst drug release. The drug release kinetics followed the non-Fickian diffusion mechanism for oil-added formulations. LO exhibited high antimicrobial activity against Porphyromonas gingivalis and Staphylococcus aureus. The DH-loaded rosin in situ forming gel with an addition of LO (0, 2.5, 5, and 10% w/w) inhibited all tested microorganisms. Adding 10% LO to rosin-based in situ forming gel improved the antimicrobial activities, especially for the P. gingivalis and S. aureus. As a result, the study demonstrates the possibility of using an LO amount of less than 10% loading into a rosin-based in situ forming gel for efficient periodontitis treatment.

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Section: Introductionmentioning

confidence: 99%

Lime Peel Oil–Incorporated Rosin-Based Antimicrobial In Situ Forming Gel

Khaing

Mahadlek

Okonogi

et al. 2022

Gels

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“…These copolymer chains exist in unimer form at concentration below critical micelle concentration (CMC) but start to self-assemble into a spherical micellar structure when its solution concentration exceeds the CMC or the solution temperature is increased above the critical micelle temperature (CMT) [ 31 , 37 ]. The formation of micelle occurs due to dehydration of the hydrophobic polypropylene oxide repeat units and defines the first step of gelation [ 38 , 39 ]. The core of micelles consist of a hydrophobic polypropylene oxide central core with their hydrophilic polyethylene oxide chains facing the external medium.…”

Section: Discussionmentioning

confidence: 99%

Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives

et al. 2021

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The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Ungual penetration enhancers (PEs) were screened based on the hydration enhancement effect to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel (P407: 27.32% w/w, ethanol: 3.18% w/w and TGA: 4.72% w/w), prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

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“…54,55 Thus, the combination of Pluronic ® F-127 and chitosan was used to reduce the individual requirement and to promote gelling at lower individual concentration in the periodontal cavity. 11 The gel strength of Az-MO-1.5-G, Az-MO-2.5-G and Az-MO-3.5-G was found to be 45 ± 3 s, 47 ± 3 s and 51 ± 3 s respectively. The data indicate that, the gel strength was sufficient to prolong the residence time in the periodontal packet for sustained drug delivery.…”

Section: Texture Profile Analysismentioning

confidence: 91%

“…13 Aithal et al, 2018 designed in situ nanoemulgel to deliver quercetin and observed 6 h prolong release profile. 14 In this study, the combination of Pluronic ® F-127 (14% w/v, thermosensitive) and chitosan (0.6% w/v, mucoadhesive and pH induced thickening polymer) was used according to the previously reported literature, 11 to reduce the individual polymer concentration in the gelling system. To extend the release of drug from the in situ gel for >12 h, lipid liquid-crystalline nanoparticles called cubosomes was used.…”

Section: Introductionmentioning

confidence: 99%

“…10 Ranch et al, 2021 used combination of Poloxamer and chitosan to optimize doxycycline loaded in situ gel to treat periodontitis. 11 Bansal et al, 2018 developed thermoresponsive in situ gel using Poloxamer and chitosan to deliver metronidazole and levofloxacin and noted sustained release for 7 h to treat periodontitis. 12 Sheshala et al, 2019 used HPMC and Poloxamer to develop moxifloxacin loaded in situ gel and observed 8 h sustain release in the in vitro study.…”

Section: Introductionmentioning

confidence: 99%

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Sustained release of azithromycin from lipid liquid-crystalline nanoparticles laden in situ gel for the treatment of periodontitis:In vitroand efficacy study

Zheng

Zhang

2022

J Biomater Appl

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Periodontitis is a chronic inflammatory disease affecting teeth, periodontal ligament and alveolar bone. Current treatment options include surgery or oral antibiotics. Oral dosage forms shows systemic side effects due to frequent dosing and it failed to reach the therapeutic concentration in the periodontal cavity. In this work, a novel in situ gel loaded with azithromycin laden lipid liquid-crystalline nanoparticles (cubosomes) was formulated for effective treatment of periodontitis. Cubosomes were prepared using DL-α-monoolein (MO) and Pluronic®F-127, and characterized for size, zeta potential, shape, and entrapment efficacy. In situ gel laden cubosomes were evaluated for pH, drug content, viscosity, syringeability, mucoadhesive strength, texture profile, gelation temperature, gel strength, in vitro release profile, antimicrobial activity and in vivo efficacy in rat model. Cubosomal size (137–450 nm) and entrapment efficacy (74–88%) increases with increase in the level of MO. The in situ gel-cubosomal batches showed sufficient viscosity (878–956 cp), syringeability (125–150N), mucoadhesive strength (25.7–26.2 dyne/cm2), gelation temperature (34.3–35.3oC), gel strength (45–51 s), and texture profile for periodontal application. The in vitro release profiles showed sustain azithromycin release for 24h from the in situ gel-cubosomal gels compared to 4h from the marketed azithromycin gel. The in vivo studies (alveolar bone loss and histopathology) in rat model confirmed the efficacy of in situ gel to treat periodontitis at low frequency of dosing compared to marketed gel. In conclusion, the study demonstrated the potential of cubosomes to sustain the release of azithromycin from in situ gelling system for effective treatment of periodontitis.

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Tailored Doxycycline Hyclate Loaded In Situ Gel for the Treatment of Periodontitis: Optimization, In Vitro Characterization, and Antimicrobial Studies

Cited by 25 publications

References 60 publications

Lime Peel Oil–Incorporated Rosin-Based Antimicrobial In Situ Forming Gel

Lime Peel Oil–Incorporated Rosin-Based Antimicrobial In Situ Forming Gel

Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives

Sustained release of azithromycin from lipid liquid-crystalline nanoparticles laden in situ gel for the treatment of periodontitis:In vitroand efficacy study

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