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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 exponent >0.43 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. [ABSTRACT FROM AUTHOR]

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 <50 μm, entrapment efficiency >80%, in-vitro drug release (T 80% ) >7 days and acceptable mucoadhesion. Further, MLIG were optimized for gelation temperature of 34–37 °C and viscosity <1000 cps respectively. FTIR, DSC and XRD graphs disclosed compatibility and alterations in crystallinity of drugs. In-vitro dissolution study demonstrated non-Fickian type of drug release mechanism for twelve days. Stability studies ascertained MLIG implants were sterilizable and stable for about 11.29 months on refrigeration. The formulations exhibited significant (p < 0.001) antimicrobial activity against Staphylococcus aureus , Escherichia coli , and Enterococcus faecalis , and were found biocompatible and biodegradable during preclinical studies. Ligature-induced periodontal rat model, corroborated significant growth (p < 0.05) of gingival tissue after two weeks. Clinical trials revealed, intra-pocket administration of MLIG along with SRP provided significant reduction in clinical parameters as compared to SRP alone. Conclusively, antimicrobials incorporated thermosensitive, biodegradable, mucoadhesive and syringeable MLIG implants appeared as better option for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

We have prepared tinidazole (TNZ) functionalized biodegradable chitosan (CH)/poly (ε-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 ± 8.5 nm 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 18 days, 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 < 0.05) decrease in clinical markers of periodontitis. [ABSTRACT FROM AUTHOR]

Cromolyn sodium (CS), a mast cell stabiliser, is widely employed for the prevention and treatment of allergic conditions. However, high hydrophilicity and poor oral permeability hinder its oral clinical translation. Here, solid lipid nanoparticles (SLNs) have been developed for the purpose of oral bioavailability enhancement. The CS–SLNs were engineered by double emulsification method (W1/O/W2) and optimised by using Box–Behnken experimental design. The surface and solid-state characterisations revealed the presence of CS in an amorphous form without any interactions inside the spherical-shaped SLNs. Thein-vitrorelease study showed an extended release up to 24 hr by diffusion controlled process.Ex-vivoandin-vivointestinal permeation study showed ∼2.96-fold increase in permeability of CS by presentation as SLNs (p < 0.05). Further,in-vivopharmacokinetic study exhibited ∼2.86-fold enhancements in oral bioavailability of CS by encapsulating inside SLNs, which clearly indicate that SLNs can serve as the potential therapeutic carrier system for oral delivery of CS. [ABSTRACT FROM PUBLISHER]

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 (W 1 /O/W 2 ). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]