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Objective: The goal of this research was to optimize and evaluate an intrapocket dental film, composed of polycaprolactone and carbopol blends for the management of periodontitis. Methods: The intrapocket dental film was prepared using a modified solvent casting method, followed by characterization, in-vitro release, in-vitro antimicrobial activity, and in-vivo efficacy on the periodontitis animal model. Results: Prepared films were consistent in thickness (2.10±0.56 to 2.50±0.39 mm) and weight (35.23±0.37 to 39.45±0.45 mg) with drug entrapment of up to 87.63±1.98 percent. The concentration of carbopol is observed to have a direct relationship with the thickness, film weight, and swelling factor of the prepared dental film. The film has a surface pH close to gingival crevicular fluid pH and is therefore appropriate for the application. The developed film exhibited a biphasic drug release profile with an initial burst release followed by a continuous release for more than 11 days. Drug release kinetic study supports the release of the drug by a diffusion-based process, as best explained by the Korsmeyer Peppas kinetics (R2 =0.9635). in vitro antimicrobial activity was also in accordance with drug release, with a high initial zone of inhibition (ZOI) (49.32±0.156mm), followed by 14.28±0.080 mm ZOI on the 11th day. The in vivo study showed that the prepared film was able to prevent periodontal ligament degeneration, as observed in the periodontitis experiment animal model. Conclusion: The prepared intrapocket dental film based on caprolactone and carbopol can be used as a novel local drug delivery system for the management of periodontitis.

Considering alarming projections in the prevalence of periodontitis, following study was undertaken to develop chitosan-vanillin crosslinked microspheres loaded in-situ gel (MLIG) implants containing ornidazole and doxycycline hyclate for the treatment of pocket infections. Firstly, microspheres were formulated and optimized using response surface methodology for particle size 80%, in-vitro drug release (T80%) >7 days and acceptable mucoadhesion. Further, MLIG were optimized for gelation temperature of 34–37 °C and viscosity

Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis.Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis.The film was developed by using solvent casting technique and "Design of Experiments" approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior.Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days.The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.

We have prepared tinidazole (TNZ) functionalized biodegradable chitosan (CH)/poly (e-caprolactone) (PCL) mucoadhesive hybrid nanofiber membrane (TNZ-PCHNF) to alleviate existing shortcomings in treatment of periodontitis. Box-Behnken design was employed for evaluating influence of formulation and processing variables on quality of final formulation. Optimized nanofiber membrane was subjected to solid-state and surface characterization studies using FTIR, DSC, XRD, SEM and AFM, which revealed that TNZ was entrapped in an amorphous form inside smooth and uniform cylindrical nanofibers without any physicochemical interaction with excipients. The optimized TNZ-PCHNF membrane had a diameter of 143.55±8.5nm and entrapment efficiency of 83.25±1.8%. In vitro drug release and antibacterial study demonstrated capability of the developed nanofiber membranes for efficiently delivering TNZ in a sustained manner up to 18days, and its ability to inhibit bacterial growth, respectively. Further, reduction of contact angle (from 123.4±2.5 to 27.4±2.3) revealed that blending of CH with PCL increases hydrophilicity of the nanofiber membrane. MTT assay and CLSM study suggested that nanofiber membrane was devoid of cytotoxicity on mouse fibroblasts. Moreover, preliminary clinical trials on patients proved therapeutic efficacy of the nanofiber membrane by eliciting a significant (p

Periodontal disease is chronic, highly prevalent infectious disease that requires prolonged and controlled delivery of antimicrobial agents into pockets. To achieve this objective, dual antimicrobials encapsulated chitosan fortified calcium alginate (CS-Ca-SA) microspheres were formulated by application of Plackett-Burman factorial design. The microspheres were optimized for particle size (PS), entrapment efficiency (EE) and drug release. The optimized microspheres presented average PS of 74-461 µm and EE of 62.45-86.20% with controlled drug delivery for 120 hours. FTIR disclosed successful complexation between SA and CS. DSC and XRD studies showed changes in the crystallinity of drugs in microspheres. Shape factor and SEM demonstrated spherical to pear-shaped microspheres. Release exponent0.43 and high diffusion coefficients revealed non-Fickian-based diffusion-limited drug release. CS-Ca-SA microspheres exhibited surface pH of 6.5 ± 0.5, moderate swelling, less erosion and improved mucoadhesion over Ca-SA microspheres. Also, significant antimicrobial activity against Escherichia coli and Staphylococcus aureus and cytocompatibility with L929 cell lines were observed. Further, microspheres exhibited long-term stability on refrigeration. The outcomes of study supported the potential of dual polymer and dual drug-based biodegradable, stable, non-toxic, mucoadhesive, controlled and prolonged drug release microspheres as more patient compliant by administration into periodontal pockets for the management of periodontal disease.

An open wound is highly susceptible to microbial infection leading to elevated level of inflammatory response. For prompt healing, a wound requires a biomimetic dressing material with ideal hydrophilicity and tensile strength, possessing antimicrobial and antioxidant property. Although PCL-based nanofibers have sufficient tensile strength and biocompatibility, it lacks in terms of optimum hydrophilicity and biodegradation. Therefore, we fabricated a PCL-gelatin based electrospun nanofibers, enriched with quercetin and ciprofloxacin hydrochloride (CH). The average diameter of developed nanofibers was 725.943 ± 201.965 nm, and devoid of chemical interaction between two drugs and polymers. CH and quercetin exhibited biphasic in-vitro release in phosphate buffer (pH 7.4). The in-vitro antibacterial and antioxidant property of scaffolds were evaluated by film-diffusion against Staphylococcus aureus and DPPH assay, respectively. The addition of gelatin along with CH and quercetin enhanced the hydrophilicity (contact angle = 48.8 ± 2.95°) and biodegradation rate of the nanofibers. In-vitro biocompatibility of scaffold was examined by hemocompatibility and fibroblast viability using MTT assay. The results confirm the direct application of scaffold in the wounded area. Further, complete closure of full-thickness wound within 16 days, and regulation of hydroxyproline, SOD and catalase level in granulation tissues following treatment with scaffold, confirmed its application for accelerated wound healing.

High hydrophilicity curtails the intestinal permeation of cromolyn sodium (CS) which in turn compels to compromise with its multiple biological activities. Hence, the present research was intended with an objective to develop CS encapsulated polylactide-co-glycolide (PLGA) nanoparticles (CS-PNs) for enhancing intestinal permeation. The CS-PNs were prepared by double emulsification solvent evaporation method (W1/O/W2). The "Quality by Design" approach using box-behnken experimental design was employed to enhance encapsulation of CS inside CS-PNs without compromising with particle size. The polymer concentration, surfactant concentration and organic/aqueous phase ratio significantly affected the physicochemical properties of CS-PNs. The optimized CS-PNs were subjected to various solid-state and surface characterization studies using FTIR, DSC, XRD, TEM and AFM, which pointed towards the encapsulation of CS inside the spherical shaped nanoparticles without any physical as well as chemical interactions. Ex-vivo intestinal permeation study demonstrated ∼4 fold improvements in CS permeation by forming CS-PNs as compared to pure CS. Further, in-vivo intestinal uptake study performed using confocal microscopy, after oral administration confirmed the permeation potential of CS-PNs. Thus, the findings of the studies suggest that CS-PNs could provide a superior therapeutic carrier system of CS, with enhanced intestinal permeation.

Background: Glaucoma is the leading cause of irreversible blindness worldwide. It is very important to diagnose glaucoma in early stages so that timely management can be done. Spectral domain optical coherence tomography (SD-OCT), is a newer device which helps to diagnose glaucoma early. The aim of our study was to evaluate the RNFL, ONH, and mGCA (GCL+IPL) measurements for early glaucoma detection using spectral domain optical coherence tomography (SD-OCT).Methods: Total 30, POAG (primary open angle glaucoma) suspects were compared with 30 normal controls. The Cirrus HD-OCT optic disc cube 200 × 200 protocol was used to measure ONH, RNFL and macular parameters.Results: The average cpRNFL thickness of all quadrants was significantly lower in POAG suspects, (84.13±7.42 μm versus 103.85±8.95 μm, p

Microbial infection and oxidative damage of the fibroblast often results in prolonged and incomplete wound healing. Therefore, there is an increasing demand for a scaffold being effective to prevent any possible infection and neutralize excessively released free radicals. Herein, we designed a PCL-based nanofiber loaded with ciprofloxacin hydrochloride (CHL) and quercetin. Developed nanofiber showed the formation of smooth and continuous nanofiber with 101.59 ± 29.18 nm average diameter and entrapping the drugs in amorphous form without any possible physico-chemical interaction between drugs and excipient. High entrapment efficiency (CHL: 92.04% and Que: 94.32%) and prolonged in-vitro release (for 7 days) demonstrated the capability of scaffold to suppress any probable infection and oxidative damage, which was further confirmed by in-vitro antibacterial and antioxidant activity. The biocompatibility of scaffold for direct application to wound site was evaluated through hemocompatibility and cytocompatibility assay. The wound healing efficacies of nanofiber were assessed using full thickness wound model in rats, which displayed accelerated wound healing with complete re-epithelialization and improved collagen deposition within 16 days. In-vivo wound healing finding was further corroborated by SOD, catalase, and hydroxyproline assay. The current study validates the application of ciprofloxacin HCl and quercetin functionalized nanofiber as a potential wound dressing material.

The aim of this study was to alleviate shortcomings in the treatment of periodontitis by electrospinning of a novel biodegradable poly(e-caprolactone) (PCL) based nanofiber membrane functionalized with tinidazole (TNZ). Box–Behnken design was employed for evaluating influence of formulation and processing variables on entrapment efficiency (EE) and diameter of nanofiber. The optimum batch selected by desirability approach was subjected to physicochemical characterization such as FTIR, DSC and PXRD which revealed entrapment of drug in a molecular dispersion devoid of any chemical interaction with the excipients. Electron microscopy showed smooth structure in nanometre range, without any visible sign of fiber break-up or disruption within the nanofiber membrane. Optimized TNZ-PCL nanofiber membrane exhibited a diameter of 147.6 ± 7.6 nm and EE 84.36 ± 1.5%. In vitro release study and antibacterial study demonstrated sustained drug release for up to 20 days, depending upon the drug to polymer ratio and solvent composition. Further, reduction of contact angle (from 123.6 ± 2.8 to 57.2 ± 1.9) revealed that incorporation of TNZ enhanced the hydrophilicity of the nanofiber membrane which would facilitate its adhesion to the site of action and instigate proliferation of cells. MTT assay and CLSM study suggested that nanofiber membrane showed no cytotoxicity on mouse fibroblasts (L-929 cell lines). Moreover, in vivo study by ligature-induced periodontitis in rats confirmed that TNZ loaded nanofiber membrane can significantly (p < 0.05) improve continuity of epithelium and transseptal fiber of interdental papilla in comparison to tinidazole gel.

The aim of the present study was to prepare atorvastatin calcium (ATR) loaded poly(e-caprolactone) nanoparticles (ALPNs) to enhance the oral bioavailability, efficacy and safety profile of drug. ALPNs were prepared by a nanoprecipitation technique while formulation and process parameters were optimized using a central composite factorial design. The optimized ALPNs were investigated through in vitro (solid state characterization, morphological, drug release study and stability study) analysis and in vivo (pharmacokinetic, efficacy and safety study) behaviour in rats. The optimized ALPNs having 197 ± 5 nm particle size, 0.213 ± 0.012 polydispersity index and 75.6 ± 3.2% entrapment efficiency, did not exhibit any physicochemical interaction of the drug with the carrier. The X-ray diffraction, differential scanning calorimetry and electron diffraction pattern has substantiated the amorphous character of ATR encapsulated in nanoparticles. The smooth and homogeneous spherical shape of the nanoparticles was evidenced in morphological analyses. The in vitro drug release profile of ALPNs showed a 96 h sustained release and the pharmacokinetic profile in rats exhibited significant enhancement in bioavailability, Cmax and mean resident time of the drug. ALPNs exhibited similar efficacy (plasma lipid profile and glucose level) and markedly improved biochemical safety profiles (creatinine, blood urea nitrogen, creatinine kinase, lactate dehydrogenase and aspartate amino transferase) of rat plasma at a 50% reduced dose compared to orally administered ATR.

Soluthin MD®, a unique phosphatidylcholine-maltodextrin based hydrophilic lipopolysaccharide, which exhibits superior biocompatibility and bioavailability enhancer properties for poorly water soluble drug(s). Curcumin (CUR) is a potential natural anticancer drug with low bioavailability due to poor aqueous solubility. The study aims at formulation and optimization of CUR loaded lipopolysaccharide nanocarriers (C-LPNCs) to enhance oral bioavailability and anticancer efficacy in colon-26 tumor-bearing mice in vitro and in vivo. The Optimized C-LPNCs demonstrated favorable mean particle size (108 ± 3.4 nm) and percent entrapment efficiency (65.29 ± 1.0%). Pharmacokinetic parameters revealed ∼130-fold increase in oral bioavailability and cytotoxicity studies demonstrated ∼23-fold reduction in 50% cell growth inhibition when treated with optimized C-LPNCs as compared to pure CUR. In vivo anticancer study performed with optimized C-LPNCs showed significant increase in efficacy compared with pure CUR. Thus, lipopolysaccharide nanocarriers show potential delivery strategy to improve oral bioavailability and anticancer efficacy of CUR in the treatment of colorectal cancer.

Increased prevalence of oral diseases such as gingivitis, periodontitis and dental caries has become major health issue worldwide. Such growing incidence of periodontitis has directly affected the development of drug delivery systems and growth of the market. Since the infections are limited to periodontal pockets or oral cavity, localized intrapocket drug delivery will be more beneficial than conventional systemic administration. Advances in intrapocket technology and innovations in the field of periodontal drug delivery led to increased patent applications. Newer trends like use of mucoadhesive polymers, in situ forming gels, viscosity modifiers, plasticizers etc which can enhance intrapocket retention of drugs have gained considerable attention among researchers and industrialists. Current market is flooded with products such as Periostat, Periochip(®), Atridox(®), Arestin(®), Actisite(®), Dentomycin(®), and Elyzol(®) and generics such as metronidazole, levofloxacin, tetracycline, doxycyline and minocycline for intrapocket delivery. There is a need of novel drugs and delivery systems with better efficacy profiles than the existing compounds. Inclusion of novel technologies like films, fibers, in situ forming implants, microparticles, nanoparticles, and liposomes as intrapocket drug delivery has great potential. Development of antibiotic free drug delivery such as antiseptics, host modulators, biofilms inhibitors and antibodies has promising role in the improvement of pathogenesis of periodontitis. Further, this review deals with various innovations in drug delivery and patents related to localized intrapocket administration of medicaments in the implications of periodontitis.

In the present study, cromolyn sodium (CS), a highly water soluble molecule was encapsulated into rationally designed, core–shell polymeric-lipid hybrid nanoparticles (PLHNs) for enhancing its oral bioavailability, by improving its intestinal permeability through lymphatic uptake. The CS encapsulated PLGA–lecithin based core–shell PLHNs (CS–PLHNs) were engineered by a double emulsification solvent evaporation method and optimized using a response surface methodology based “Quality by Design” approach. The Box–Behnken experimental design was imperatively enforced to enhance encapsulation of CS inside PLHNs without compromising particle size. Optimized CS–PLHNs exhibited a particle size of 227 ± 3.8 nm and EE of 57.8 ± 1.32% with unimodal size distribution. The physico-chemical characterizations of CS–PLHNs suggested the encapsulation of CS in an amorphous form inside PLHNs without any interactions. The morphological studies pointed towards the existence of smooth, spherical core–shell architecture of CS–PLHNs, which extended release up to 48 h by a controlled diffusion process. The optimized CS–PLHNs exhibited remarkable stability at different environmental conditions as well as in biological milieu. An ex vivo intestinal permeation study showed that the permeation of CS was significantly improved by encapsulating it inside PLHNs compared to that of pure CS, which was additionally confirmed by the in vivo intestinal uptake study using confocal microscopy. A pharmacokinetic study in rats further exhibited 11.9 fold enhancement in the oral bioavailability of CS after its incorporation into PLHNs. In a nutshell, PLHNs can serve as a superior therapeutic carrier system by imparting lipophilicity to potentially obtain the high oral bioavailability of CS, which can further be extended towards numerous hydrophilic drug molecules.

This study aimed to formulate and characterizeMedicatedThe 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 conclusion, optimized 1.5% w/v chitosan

Application of Plackett-Burman factorial design to investigate the effect of processing factors in the fabrication of ionically crosslinked chitosan-tripolyphosphate (CS-TPP) microspheres.Microspheres were screened and optimized to provide maximum process yield (PY), encapsulation efficiency (EE), and time for 80% drug release (TProcessing factors viz. method of preparation (MOP), CS, TPP, crosslinking time (CT), agitation (AS), and drying technique (DT) were selected. Solid state characterization was performed by Fourier-Transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Mucoadhesion, cytocompatibility, and stability of microspheres were also evaluated.Pareto analysis and analysis of variance, screened most significantly (p .05) impacting process factors on selected responses. The optimized microspheres demonstrated: o/w emulsification method, CS (2.5%), TPP (5%), CT (120 min), AS (2000 rpm), and DT (freeze-dried), and provided PY- 95.67%, PS- 168.45%, EEOZ- 85.56%, EEDX- 91.34%, BOZ- 15.26%, BDX- 12.91%, TOZ- 47.09 and TDX- 67.95 minutes. FTIR illustrated compatibility between excipients and complexation of CS and TPP. XRD and DSC showed loss of crystallinity of entrapped drugs in microspheres. Biphasic drug release was observed for four days with non-Fickian kinetics. Furthermore, microspheres exhibited good mucoadhesivity (82.51%), antimicrobial activity against Staphylococcus aureus and Escherichia coli, cytocompatibility for L929 cells, and long-term stability.Therefore, CS-TPP microspheres were found mucoadhesive, safe, stable and provided controlled and prolonged release of drugs. These properties confirmed its high potential and applicability in chronic periodontitis.

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Metronidazole (MZ) and levofloxacin (LF) are widely employed for treatment of periodontitis, but high oral dose and resistance development after long-term oral administration limit their use. The aim of this study was to alleviate shortcomings in the treatment of periodontitis by fabrication of intrapocket, biodegradable films of chitosan (CS) loaded with MZ and LF meant for inserting into periodontal pockets to treat infections. The films were developed by solvent casting technique using propylene glycol as plasticizer and glutaraldehyde as crosslinking agent. Their physical characteristics, such as drug content, surface pH, swelling index, and folding endurance, exhibited results within limit. Further, FTIR and DSC studies revealed stability of films and compatibility between drugs and excipients. SEM images of films showed the presence of free drug particles on the surface causing burst effect. In vitro release in McIlvaine buffer pH 6.6 was of sustained nature assisted by the burst effect. CS and crosslinking agent concentrations negatively affected drug release and positively affected T90 (time for releasing 90% of the drug) due to altered matrix density. In contrast, the plasticizer concentration increases membrane permeability and hence increased drug release, lowering T90. Crosslinked films demonstrated sustained release up to 7 days. The antibacterial efficacy of films was tested on Staphylococcus aureus and Escherichia coli, indicating good antibacterial activity. Clinical trials on patients proved the therapeutic efficacy of the films by a significant (p