Thermoreversible Gels Research Articles

Thermo-Reversible Gelation of Aqueous Hydrazine for Safe Storage of Hydrazine

A reversible gelation–release system was developed for safe storage of toxic hydrazine solution based on gelation at lower critical solution temperature (LCST). Poly(N-isopropylacrylamide) (PNIPAM) and its copolymer could form gels of 35wt% hydrazine by dissolution under low temperature and storage at ambient temperatures. For example, PNIPAM gelled a 63 fold heavier amount of 35wt% hydrazine. Aqueous hydrazine was released from the gels by compression or heating, and the gelation–release cycles proceeded quantitatively (> 95%). The high gelation ability and recyclability are suitable for rechargeable systems for safe storage of hydrazine fuels.

Effects of surface area and porosity on behavior of IL molecules in meso and macroporous polymeric networks

In this work, ionogels fabricated by incorporating room temperature ionic liquids (ILs) in meso- and macroporous syndiotactic polystyrene (sPS) gels, are studied by using differential scanning calorimetry (DSC), polarized optical microscopy (POM), rheology, and nuclear magnetic resonance (NMR) spectroscopy. sPS gel network is prepared via thermo-reversible gelation in tetrahydrofuran and the pores are subsequently filled with the ionic liquid, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (PYR14TFSI). Using DSC and POM it is found that PYR14TFSI molecules in sPS gels show higher melting temperatures than that for the neat PYR14TFSI. 1H static NMR signals provide overall mobility of ILs in the sPS gels. Surprisingly, the ionogel prepared with 0.04 g/mL sPS solution apparently shows the broadest 1H NMR signals among the gels prepared with 0.04, 0.08, and 0.12 g/mL sPS concentration. This is attributed to a quasi-bulk state of ILs. Moreover, two-dimensional 1H NOESY spectra indicate that PYR14TFSI molecules in sPS show strong non-bonded through-space correlation peaks and their intensities increase proportionally with polymer concentration in the gel, while such correlation peaks are not observed for the neat PYR14TFSI molecules. The observed concentration dependence of constrained PYR14TFSI dynamics is interpreted in terms of the confined PYR14TFSI at the surface or closer to the surface of sPS scaffold. From these experimental results, it is suggested that PYR14TFSI melting-temperature are more related to quasi-bulk component than the constrained PYR14TFSI in the sPS gels.

Gene cloning, expression enhancement in Escherichia coli and biochemical characterization of a highly thermostable amylomaltase from Pyrobaculum calidifontis

Pcal_0768 gene encoding an amylomaltase, a 4-α-glucanatransferase belonging to family 77 of glycosyl hydrolases, from Pyrobaculum calidifontis was cloned and expressed in Escherichia coli. The recombinant protein was produced in E. coli in soluble and active form. However, the expression level was not very high. Analysis of the mRNA of initial seven codons at the 5′-end of the gene revealed the presence of a hair pin like secondary structure. This secondary structure was removed by site directed mutagenesis, without altering the amino acids, which resulted in enhanced expression of the cloned gene. Recombinant Pcal_0768 exhibited optimal amylomaltase activity at 80 °C and pH 6.9. Under these conditions, the specific activity was 690 U/ mg. Recombinant Pcal_0768 was highly thermostable with a half-life of 6 h at 100 °C. It exhibited the highest kcat value among the characterized glucanotransferases. No metal ions were required for activity or stability of the enzyme. Recombinant Pcal_0768 was successfully employed in the synthesis of modified starch for producing thermoreversible gel. To the best of our knowledge, till now this is the most thermostable enzyme among the characterized amylomaltases. High thermostability and starch modification potential make it a novel and distinct amylomaltase.

Thermoreversible Polymer Gels in DMF Formed from Charge- and Crystallization-Induced Assembly.

Polymer organogels formed through dynamic interactions are interesting for various applications. The fabrication of polymer organogels in polar solvents through ionic interaction is rare, although such organogels in non-polar organic solvents have been well studied. Herein, polymer organogels in a polar solvent N,N-dimethyl formamide (DMF) were fabricated from a triblock copolymer, poly(4-vinyl pyridine)-block-poly(ethylene glycol)-block-poly(4-vinyl pyridine) (4VPm-EGn-4VPm), and a fluorinated surfactant, perfluorooctanoic acid (PFOA), and their microphase separation and properties were studied. Ordered microphase separation and the crystalline structures were revealed by small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), respectively. All the 4VPm-EGn-4VPm/PFOA organogels are sensitive to temperature, and the ratio of PFOA to pyridine groups reversibly. The polymer organogels are also responsive to triethylamine and triethylammonium acetate.

Understanding the Molecular Structure of the Elastic and Thermoreversible AlCl3 : Urea/Polyethylene Oxide Gel Electrolyte.

It is possible to prepare elastic and thermoreversible gel electrolytes with significant electroactivity by dissolving minimal weight fractions of ultra-high molecular weight polyethylene oxide (UHMW PEO) in an aluminum deep eutectic solvent (DES) electrolyte composed of AlCl3 and urea at a molar ratio of 1.5 : 1 (AlCl3 /urea). The experimental vibrational spectra (FTIR and Raman) provide valuable information on the structure and composition of the gel electrolyte. However, the complexity of this system requires computational simulations to help interpretation of the experimental results. This combined approach allows us to elucidate the speciation of the DES liquid electrolyte in the gel and how it interacts with the polymer chains to give rise to an elastic network that retains the electroactivity of the liquid electrolyte to a very great extent. The observed reactions occur between the ether in the polymer and both the amine groups in urea and the aluminum species. Thus, similar elastomeric gels may likely be prepared with other aluminum liquid electrolytes, making this procedure an effective way to produce families of gel aluminum electrolytes with tunable rheology and electroactivity.

Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels

Synthetically modified proteins, such as gelatin methacryloyl (GelMA), are growing in popularity for bioprinting and biofabrication. GelMA is a photocurable macromer that can rapidly form hydrogels, while also presenting bioactive peptide sequences for cellular adhesion and proliferation. The mechanical properties of GelMA are highly tunable by modifying the degree of substitution via synthesis conditions, though the effects of source material and thermal gelation have not been comprehensively characterized for lower concentration gels. Herein, the effects of animal source and processing sequence are investigated on scaffold mechanical properties. Hydrogels of 4-6 wt% are characterized. Depending on the temperature at crosslinking, the storage moduli for GelMA derived from pigs, cows, and cold-water fish range from 723 to 7340 Pa, 516 to 3484 Pa, and 294 to 464 Pa, respectively. The maximum storage moduli are achieved only by coordinated physical gelation and chemical crosslinking. In this method, the classic thermo-reversible gelation of gelatin occurs when GelMA is cooled below a thermal transition temperature, which is subsequently "locked in" by chemical crosslinking via photocuring. The effects of coordinated physical gelation and chemical crosslinking are demonstrated by precise photopatterning of cell-laden microstructures, inducing different cellular behavior depending on the selected mechanical properties of GelMA.

Autoclaving of Poloxamer 407 hydrogel and its use as a drug delivery vehicle.

With antibiotic-resistant bacteria becoming increasingly prevalent, biomaterials capable of targeted, in situ drug delivery are urgently needed. The synthetic polymer Poloxamer 407 (P407) is of particular interest due to its thermoreversible gelation. Clinical use of P407 typically involves sterilization via autoclaving, but the effects of these extreme environmental conditions on hydrogel water content, rheological properties and efficacy as a drug delivery vehicle remain unknown. The aim of this study was to investigate the effects of autoclaving on the properties of P407 hydrogel. Autoclaving reduced hydrogel water content due to evaporation, thus increasing the polymer weight fraction of the hydrogels. In contrast, except for a reduction in gelation temperature following autoclaving, autoclaved hydrogels had similar rheological properties as nonautoclaved hydrogels. In vitro, autoclaving did not hinder the hydrogel's efficacy as a carrier for vancomycin antibiotic, and P407 (with and without vancomycin) had a bactericidal effect on planktonic Staphylococcus aureus. An in vivo pilot study using P407 to deliver bacteriophage highlighted the need for additional understanding of the functionality of the hydrogel for surgical applications. In conclusion, P407 hydrogel water content and gelation temperature were reduced by autoclave sterilization, while other rheological properties and the efficacy of the biomaterial as a delivery vehicle for vancomycin in vitro were unaffected.

Hybrid materials from tri-aryl amine organogelators and poly[vinyl chloride] networks

Hybrid thermoreversible gels have been prepared from polyvinyl chloride (PVC) and tri-aryl tri-amines organogelators (TATA-C11) in bromobenzene. A thermodynamic investigation by DSC has shown that the TATA-C11 formation and melting temperatures are not altered by the presence of PVC chains, nor are the formation and melting enthalpies. Scanning electron microscopy observations have revealed as each network are clearly distinguished, so that the hybrid gel is simply a combination at the micron level of both original gels. X-ray diffraction experiments have shown that the TATA-C11 structure in bromobenzene differs from its solid state, and is rather reminiscent of a hexatic phase, possibly due to the occurrence of a molecular compound. The structure of the TATA-C11 moiety does not change in the hybrid gel. Finally, the rheological properties have been studied. It is observed that the modulus of the hybrid gel greatly exceeds the Voigt's upper limit (larger than a simple additivity of the moduli). This effect is examined in the light of a possible de-solvation of the amorphous part of the PVC fibrils (de-plasticization).

Thermal stability of prepared chicken feet gelatine gel in comparison with commercial gelatines

Gelatine is, due to its functional properties, currently widely used not only in the food industry (in the production of confectionery, dairy products, canned food) but also in pharmacy (soft and hard capsules) and cosmetics (creams, lotions) where it applies its ability to form thermoreversible gel stronger than most other gelling agents. What is more, it provides further excellent properties including emulsifying, foaming, stabilizing, film-forming, water and fat binding, texturizing, thickening, and adhesive attributes which makes it a very important hydrocolloid. Gelatine is obtained from the raw material of animal tissues containing collagen, usually mammalian skin or bones. For religious reasons in some countries, pork or bovine gelatine must be replaced by an alternative form, such as poultry or fish gelatine. The quality of gelatine is assessed mostly by the strength of gelatine gel which strongly depends on ambient temperature or humidity. Extraction conditions may also significantly affect the quality of gelatine. This study examined possible changes in the strength of gelatine gels prepared from laboratory-produced chicken feet gelatine and compared them with commercially available pork and beef gelatines at temperatures of 23, 29, and 35 °C at 60 and 80% humidity. While at 23 °C thermal stability of prepared chicken gelatine was monitored higher than in commercial gelatines, experiments at 29 and 35 °C provided equivalent results for chicken and commercial gelatines. Therefore, prepared chicken gelatine offers a significant potential to become an alternative to traditional gelatines. The information about gelatine gels thermal stability is of great importance for applications not only in the food; but also in the pharmaceutical industry.

Poloxamer-Based In Situ Nasal Gel of Naratriptan Hydrochloride Deformable Vesicles for Brain Targeting

Migraine is the chronic neurological disorder identified by recurrent moderate to severe headache. Research was highlighted to formulate target drug delivery to treat migraine via the olfactory lobe through the intranasal route using ethosomal thermoreversible gel. Ethosomes were prepared by thin film hydration method using 32 factorial design. The prepared ethosomes were evaluated for percent drug loading, vesicle size, zeta potential, and polydispersity index, whereas nanoethosomal in situ gels were assessed for their pH, viscosity, mucoadhesive strength, and in vitro drug release. Ex vivo drug permeation was evaluated using nasal mucosa of sheep. The data produced from the experimental design indicated NE6 (soya lecithin 3%:ethanol 50%) as the optimized ethosome formulation, whereas NG3 (carbol 934-0.3%) and NG6 (PVP K30-0.3%) were recorded as the optimized in situ gel formulations. In vitro and ex vivo drug release demonstrated almost 100% release after 24 h for optimized formulations. In conclusion, drug-loaded in situ mucoadhesive gels could release the drug for longer duration of time which can improve the bioavailability providing new dimension to the treatment of migraine.

Irreversible Shear-Activated Gelation of a Liquid Crystalline Polyelectrolyte.

We report irreversible, shear-activated gelation in liquid crystalline solutions of a rigid polyelectrolyte that forms rodlike assemblies (rods) in salt-free solution. At rest, the liquid crystalline solutions are kinetically stable against gelation and exhibit low viscosities. Under steady shear at, or above, a critical shear rate, a physically cross-linked, nematic gel network forms due to linear growth and branching of the rods. Above a critical shear rate, the time scale of gelation can be tuned from hours to nearly instantaneously by varying the shear rate and solution concentration. The shear-activated gels are distinct in their structure and rheological properties from thermoreversible gels. At a fixed concentration, the induction time prior togelation decreases exponentially with the shear rate. This result indicates that shear-activated thermalization of the electrostatically stabilized rods overcomes the energy barrier for rod-rod contact, enabling rod fusion and subsequent irreversible network formation.

Thermal Guanidine Metathesis for Covalent Adaptable Networks.

We demonstrate that a dynamic chemical reaction that we term thermal guanidine metathesis (TGM) can serve as the basis for covalent adaptable network (CAN) materials. CANs are a class of cross-linked polymers that transition from thermoset to thermoplastic-like rheological behavior upon significant activation of reversible exchange reactions within the network and thus can be reprocessed. Small molecule studies indicate the TGM reaction proceeds by a dissociative mechanism, and guanidine-cross-linked network polymers can be reprocessed at elevated temperature. These TGM-based CANs exhibit dynamic behavior, such as dissolution in the presence of monofunctional exchange partners and stress relaxation above Tg. Additionally, differences in the activation energies obtained by small molecule kinetic studies and stress relaxation analysis are consistent with key predictions of the Semenov-Rubinstein model of thermoreversible gelation of highly cross-linked networks.

Investigating the Potential to Deliver and Maintain Plasma and Brain Levels of a Novel Practically Insoluble Methuosis Inducing Anticancer Agent 5-Methoxy MOMIPP Through an Injectable In Situ Forming Thermoresponsive Hydrogel Formulation

A new indole based chalcone molecule MOMIPP induced methuosis mediated cell death in gliobastoma and other cancer cell lines. But the drug was insoluble in water and had a very short plasma half-life. The purpose of this work was to develop a formulation that can provide sustained levels of MOMIPP in vivo. Initial studies established drug solubility in various solvents. N-methyl pyrrolidone (NMP) was determined as an excellent solvent for the drug. Subsequently a poloxamer-407 based thermoreversible gel containing NMP was used to develop the formulation. Rheological studies were performed via oscillatory temperature mode, continuous shear analysis, and oscillatory frequency mode experiments. The mechanical properties of the formulations were tested using a texture profile analyzer. The gelation temperature and time of formulations increased with increasing amounts of NMP. However, the viscosity at 20 °C and storage modulus decreased as the amount of NMP increased. Characterization studies helped to identify the gel formulation that was used to administer the drug orally, sub-cutaneously, and intra-peritoneally. When the gel was given intraperitoneally the target plasma and brain levels of over 5 μM was maintained for about 8 h. Thus, a thermoreversible gel formulation that can deliver MOMIPP in animal studies was successfully developed.

Articular chondrocytes from osteoarthritic knee joints of elderly, invitro expanded in thermo-reversible gelation polymer (TGP), exhibiting higher UEA-1 expression in lectin microarray.

Autologous chondrocytes in vitro expanded, are used as tools of regenerative therapies for cartilage injuries. However, inability to maintain the hyaline phenotype both in vitro and post in vivo transplantation, remains one of the major hurdles for long term efficacy under clinical settings. We have reported earlier, hyaline phenotype maintenance of both human and rabbit chondrocytes for a long duration both in vitro when cultured conditions using a Thermo-reversible Gelation Polymer (TGP) scaffold-based methodology and in vivo post-transplantation animal model of cartilage damage. Having intrigued by such encouraging outcome, we in this study, analysed the similar TGP culture environment whether would be able to allow in vitro expansion of severe osteoarthritis affected cartilage tissue from elderly patients and evaluated the cells using lectin microarray characterization for pluripotency. Cartilage tissue were obtained from patients (n = 7; age: 60–85 years) undergoing total knee arthroplasty for severe osteoarthritis. Chondrocytes were isolated and cultured in two groups: i. conventional culture without scaffold (2D) and ii. using a TGP scaffold-based culture (3D) up to 18 weeks. In addition to earlier reported findings such as maintenance of hyaline phenotype having been confirmed in this study as well, surface glycoprotein analysis by lectin microarray demonstrated that the α1-2 Fuc recognition lectin (UEA-1) (marker reported in literature for pluripotent stem cells) was found to be more highly expressed in 3D culture compared to 2D culture and even increased over time in 3D culture. We have developed an environment where osteoarthritis affected chondrocytes from the elderly could be cultured up to 18 weeks in vitro using TGP scaffold which express pluripotent cell associated surface glycoproteins compared to the conventional methodology.

Aging of Thermoreversible Gel of Associating Polymers

We performed Langevin dynamics simulations of amphiphilic polymers that contain strongly associating stickers connected by long soluble chain segments. We explored the aging of a thermoreversible gel which is crosslinked by aggregates (clusters) of the stickers and observed a dramatic increase of their lifetime with aging. We find that the observed aging is the result of structural reorganization of the network: the number of crosslinks decreases with time as small clusters disintegrate and their stickers are reabsorbed by large clusters that grow and become more stable by forming additional intramolecular associations between their stickers.

Pre-Clinical Assessment of the Nose-to-Brain Delivery of Zonisamide After Intranasal Administration.

Zonisamide clinical indications are expanding beyond the classic treatment of epileptic seizures to Parkinson's disease and other neurodegenerative diseases. However, the systemic safety profile of zonisamide may compromise its use as a first-line drug in any clinical condition. Since zonisamide is marketed as oral formulations, the present study aimed at exploring the potential of the intranasal route to centrally administer zonisamide, evaluating the systemic bioavailability of zonisamide and comparing its brain, lung and kidney pharmacokinetics after intranasal, oral and intravenous administrations. In vitro cell studies demonstrated that zonisamide and proposed thermoreversible gels did not affect the viability of RPMI 2650 or Calu-3 cells. Thereafter, male CD-1 mice were randomly administered with zonisamide by oral (80mg/kg), intranasal or intravenous (16.7mg/kg) route. At predefined time points, animals were sacrificed and plasma and tissues were collected to quantify zonisamide and describe its pharmacokinetics. Intranasal route revealed a low absolute bioavailability (54.95%) but the highest value of the ratio between the area under the curve (AUC) between brain and plasma, suggesting lower systemic adverse events and non-inferior effects in central nervous system comparatively to intravenous and oral routes. Furthermore, drug targeting efficiency and direct transport percentage into the brain were 149.54% and 33.13%, respectively, corroborating that a significant fraction of zonisamide suffers direct nose-to-brain transport. Lung and kidney exposures obtained after intranasal administration were lower than those observed after intravenous injection. This pre-clinical investigation demonstrates a direct nose-to-brain delivery of zonisamide, which may be a promising strategy for the treatment of central diseases.

Formulation and Evaluation Thermoreversible Gel of Antifungal Agent for Treatment of Vaginal Infection

Aims: The aim this research work is to formulate and evaluate thermoreversible gel of antifungal agent Clotrimazole for treatment of vaginal infection.
 Place and Duration of Study: Department of Biopharmaceutics, Government College of Pharmacy, Karad, Maharashtra, India, between June 2009 and July 2010.
 Methodology: Different Formulations of thermoreversible gel of antifungal agent Clotrimazole were prepared by using various concentrations of ethanol, PEG 400, sodium dodecyl sulphate, polycarbophil and pluronic F 127 and pluronic F 68. The gel formulations were subjected for evaluation on the basis of rheological behaviour, mucoadhesive behaviour, in-vitro performance.
 Results: The results indicate that Polymers such as polycarbophil, PEG- 400 in various concentrations to prepare formulations were found to release drug for period over 12 hrs. Without getting dislodged. The formulations have satisfactory rheological behavior and their diffusion profile is comparable to the marketed gel formulation. Significant difference was observed in the rheological behavior of formulations. Gel strength, spreadability, mucoadhesive strength of formulation B and C were desirable. Drug diffusion of formulation B and C were 95.2% release after 11 hrs 98.5% release after 11 hrs, respectively which was good as compared to marketed formulation showing drug diffusion of 102.2% after 10 hrs.
 Conclusion: On basis of the results we concluded that developed thermoreversible gel of Clotrimazole will be better alternative to conventional dosage form Clotrimazole & will improve patient compliance.

Evaluation of Budesonide-Hydroxypropyl-β-Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis.

New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-β-CD) and poloxamers (PL) were developed for future clinical use. This study evaluated the efficacy of such novel formulations in a rat model of colitis. The PL-BUDHP-β-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5mgmL-1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5days by a rectal route, as follows: BUD 1: BUDHP-β-CD + PL407 (18%); BUD 2: BUDHP-β-CD + PL407 (20%); BUD 3: BUDHP-β-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-β-CD; C1: HP-β-CD + PL407 (18%); C2: HP-β-CD + PL407 (20%); C3: HP-β-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1β, IL-10 and endogenous glucocorticoids were obtained using ELISA. BUDHP-β-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-β-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-β-CD (p < 0.01). All formulations with BUDHP-β-CD poloxamers reduced TNF-α levels (p < 0.05). Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.

Thermo-reversible in situ forming implant with nanostructured lipid carriers (NLC) as a delivery system for the administration of estradiol valerate.

A thermo-reversible in situ forming implant, based on the combination of Pluronic® F-127 and Pluronic® F-68 with nanostructured lipid carriers (NLC), was formulated with the aim of achieving the sustained release of estradiol valerate (EV). EV-loaded NLC, prepared by the hot high-pressure homogenization technique, presented an entrapment efficiency of 90 ± 2.9%, a particle size (PS) of 122 ± 11.2nm, a polydispersity index (PDI) of 0.344 ± 0.07, and a zeta potential (ZP) of - 10.5 ± 1.3mV. Once obtained, NLC were then included in a thermo-reversible gel (EV-loaded NLC gel), which was characterized by its rheological behavior, gelation temperature, and injectability. The in vitro release tests showed that the EV-loaded NLC gel delayed the release significantly, in comparison with a solution of the drug and with the EV-loaded NLC. The EV-loaded NLC gel and a commercially available suspension containing estradiol were administered parenterally to rabbits. A 16.8-fold greater AUC and a 40-fold higher Cmax were obtained with the EV-loaded NLC gel, compared to the commercial suspension. A rapid initial release of EV in vivo, from the EV-loaded NLC gel, suggests that it is necessary to adjust the ratio of the copolymers or to include in the gel an additive that improves gelation time and gel strength, in order to achieve a sustained release. An interesting observation was that the in vitro profile, which has a three-phase behavior, coincides with what was observed in the in vivo study. Graphical abstract.

Comparative evaluation of 2% turmeric extract with nanocarrier and 1% chlorhexidine gel as an adjunct to scaling and root planing in patients with chronic periodontitis: A pilot randomized controlled clinical trial.

Context:Nanoparticles, owing to their smaller size, penetrate regions inaccessible to other delivery systems, such as periodontal pockets. Thus, the present study aimed to comparatively evaluate efficacy of 2% curcumin with nanocarrier and 1% chlorhexidine gel as a local drug delivery (LDD) in the treatment of periodontal pockets.Materials and Methods:Forty-five chronic periodontitis patients with pocket depth 5–7 mm in two or more teeth were selected. Full-mouth scaling and root planing (SRP) was done for all patients followed by random allocation to the three treatment groups, namely SRP group (Group 1), 2% curcumin with nanogel (Group 2), and 1% chlorhexidine gel (Group 3). Clinical parameter assessment and microbiological analysis of subgingival plaque samples for Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythia (Tf) was done at baseline, 21st day, and 45th day.Results:The results showed that when the two LDD agents were used as an adjunct to SRP in chronic periodontitis, there was an improvement in all clinical parameters. Evaluation of microbiological parameters also showed a significant reduction in Aa, Pg, and Tf levels. Comparison of 2% turmeric extract with a nanocarrier system with 1% chlorhexidine gel showed that both the agents had a comparable antibacterial effect on the three selected periodontopathic bacteria.Conclusion:The present study showed that both the LDD agents showed an effective improvement of clinical and microbiologic parameters. 2% curcumin delivered with a nanocarrier system showed results comparable to chlorhexidine gel and hence shows promising future as an LDD agent in the treatment of periodontal pockets.