Efficacy of polyglycolic acid sheets and fibrin glue for the prevention of post-ELPS bleeding.

OBJECTIVE: To assess the efficacy and safety of a covering method using polyglycolic acid (PGA) sheets and fibrin glue in preventing laryngopharyngeal bleeding after endoscopic laryngopharyngeal surgery (ELPS) combined with endoscopic submucosal dissection (ESD). METHODS: Twenty-one patients who underwent ELPS combined with ESD (28 resected pharyngeal carcinomas) were retrospectively evaluated. After completing ELPS combined with ESD, fibrinogen was sprayed onto the ulcer. A PGA sheet cut into 5 × 5 mm pieces that fit the size of the ELPS-induced ulcer was then placed over the ulcer and fixed in place with a fibrin glue comprising thrombin. RESULTS: The resection procedure was performed for all lesions. The median long diameter of the resected specimen was 36 mm. The rate of a resected specimen diameter >30 mm, use of anticoagulant/platelet, and macroscopic classification 0-Ⅱa were 68% (19/28), 19% (5/28), and 36% (10/28), respectively. The median time required to cover ELPS-induced ulcers using PGA sheets and fibrin glue was 10 min (range: 3-22 min). No post-ELPS bleeding, subcutaneous emphysema, or aspiration pneumonia (0/28) was observed. CONCLUSION: The covering method using PGA sheets and fibrin glue for ELPS-induced ulcers is considered to be sufficiently safe and effective in preventing post-ELPS laryngopharyngeal bleeding. This method could be useful in preventing post-ELPS bleeding in patients with head and neck cancer.

Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)-loaded chitosan-PLGA nanoparticles in the treatment of cystic echinococcosis in laboratory mice.

Albendazole is known as the drug of choice for medical treatment of cystic echinococcosis (CE). Albendazole sulfoxide (ABZ-SO), as the main active metabolite of albendazole, has low efficacy in the disease due to low water solubility and poor absorptivity. PLGA nanoparticles (NPs) enhance the dissolution of poorly soluble drugs, and chitosan (CS) coating enhances oral drug delivery of NPs. In this study, the efficacy of ABZ-SO-loaded CS-PGLA NPs in the treatment of CE was evaluated in laboratory mice. ABZ-SO-loaded CS-PGLA NPs were prepared by nanoprecipitation and characterized by dynamic light scattering method and scanning electron microscopy. Thirty mice were intraperitoneally infected by 1000 protoscoleces of Echinococcus granulosus. Ten months later, the mice were allocated into 3 groups: groups 1 and 2 were treated with ABZ-SO and ABZ-SO-loaded CS-PGLA NPs, respectively, and the mice in group 3 remained untreated as the control group. The drugs were administered by gavage for 45 days at a daily dose of 10 mg/kg. Finally, all mice were opened and the cysts were collected, counted, weighed, and measured separately. The therapeutic effect of ABZ-SO in the number, weight, and volume of the cysts were not statistically significant compared with those in ABZ-SO-loaded CS-PGLA NPs and the control group. However, the therapeutic effect of ABZ-SO-loaded CS-PGLA NPs in the weight and volume of cysts were statistically significant when compared with that in the control group (p ˂ 0.05). In conclusions, this study revealed that ABZ-SO-loaded CS-PGLA NPs could enhance the therapeutic efficacy of ABZ-SO in the treatment of CE in laboratory mice.

Polyglycolic acid sheets decrease post-endoscopic submucosal dissection bleeding in early gastric cancer: A systematic review and meta-analysis.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC). However, post-ESD bleeding remains a serious issue, particularly in patients treated with an antithrombotic agent or those have had a large mucosal resection (≥4 cm). Whether covering the ulcer bed induced by ESD with polyglycolic acid (PGA) sheets can prevent post-ESD bleeding remains to be questioned. Therefore, we performed a systematic review and meta-analysis to evaluate the effectiveness of PGA sheets on preventing post-ESD bleeding in patients with early gastric cancer (EGC) at a high risk of post-ESD bleeding. METHODS: PubMed, Cochrane Library and EMBASE databases were searched for studies on the effect of PGA sheets shielding on inpatients with EGC and at a high risk of bleeding using post-ESD bleeding rate as the primary outcome. RESULTS: Among the four included studies (212 lesions in the PGA sheet group and 208 in the control group), post-ESD bleeding rate was significantly lower in the PGA sheet group than in the control group (4.9% vs 13.7%, risk ratio [RR] 0.33, 95% confidence interval [CI] 0.18-0.72, P = 0.004). A subgroup analysis showed that the application of PGA sheets effectively reduced the post-ESD bleeding rate in patients receiving antithrombotic agents (5.5% vs 15.2%; RR 0.37, 95% CI 0.17-0.79, P = 0.01). Although the application of PGA sheets tended to decrease the post-ESD bleeding rate in patients who had undergone large mucosal resections, the difference was not significant (4.5% vs 9.6%; RR 0.52, 95% CI 0.15-1.78, P = 0.29). CONCLUSIONS: PGA sheets can effectively prevent post-ESD bleeding in patients receiving antithrombotic agents. Further studies are needed to confirm whether PGA sheets can decrease post-ESD bleeding in patients underwent large mucosal resection.

A clinical study of efficacy of polyglycolic acid patch in surgery for pneumothorax:a systematic review and meta-analysis.

OBJECTIVES: A polyglycolic acid (PGA) patch is often used in pulmonary bullae resection, but consensus has not been reached on its effect on patient recovery. The aim of the study is to conduct a systematic review and meta-analysis of studies of polyglycolic acid for bullectomy. METHODS: A comprehensive literature search was performed using ScienceDirect, EMBASE, Ovid MEDLINE, PubMed, The Cochrane Library, Scopus, and Google Scholar. Clinical trials that compared PGA versus non-PGA for bullectomy were selected. The clinical endpoints included postoperative recurrence, average postoperative air leakage, prolonged air leaks, drainage tube removal time, and postoperative hospital stay. RESULTS: A total of eight articles (1095 patients) were included. Compared to the non-PGA approach, the PGA approach was associated with lower rates of postoperative recurrence (95% confidence interval [CI]: 0.16 to 0.39, p < 0.00001),) and of prolonged air leaks (95% CI: 0.29 to 0.72, p = 0.0007); a shorter time of drainage tube removal (95% CI: - 1.36 to - 0.13, p = 0.02); The time of average postoperative air leakage, postoperative hospital stay and operative time did not show a significant difference between the two groups. CONCLUSIONS: These results suggest that the use of PGA patch might can prevent the postoperative recurrence of spontaneous pneumothorax and decrease the rates of prolonged air leaks. More large-scale, high-quality randomized controlled trials are required to confirm our finding.

Steroid injection and polyglycolic acid shielding to prevent stricture after esophageal endoscopic submucosal dissection: a retrospective comparative analysis (with video).

BACKGROUND AND AIMS: Postoperative stricture after expansive esophageal endoscopic submucosal dissection (ESD) is a severe adverse event. Previous single-arm reports have suggested that polyglycolic acid (PGA) shielding may prevent stricture. This study was performed to assess the efficacy of this method through a comparative analysis. METHODS: This is a retrospective analysis of 500 consecutive cases of esophageal ESD performed between 2002 and 2018 at the University of Tokyo Hospital. After 2013, patients with a diagnosis of superficial esophageal carcinoma covering more than half of the esophageal circumference underwent preventive treatment with either PGA shielding or steroid injection + PGA shielding after ESD. The efficacy of these methods for preventing post-ESD stricture was assessed through multivariable logistic regression analysis. RESULTS: The risk of postoperative stricture was especially high in the cervical esophagus (odds ratio [OR], 4.60; 95% confidence interval [CI], 0.65-61.09) and after total circumferential resection (OR, 3.58×103; lower bound of 95% CI, >185). Steroid injection + PGA shielding was the only method significantly effective in preventing stricture (OR, 0.30; 95% CI, 0.10-0.78; P = .009). In the relatively low-risk subgroup (excluding cervical esophageal cancer and complete circumferential resection), the postoperative stricture rates for steroid injection + PGA shielding versus PGA shielding versus control were 18.9% versus 41.4% versus 51.7%, respectively (P = .015). However, the efficacy of this was limited in extremely high-risk cases. CONCLUSION: The combination of steroid injection and PGA shielding is effective for preventing post-ESD stricture. There is a need for even more effective methods for cervical esophageal cancer and complete circumferential resection.

Differentiated adipose-derived stem cells promote peripheral nerve regeneration.

INTRODUCTION: Many reports have indicated that adipose-derived stem cells (ADSCs) are effective for nerve regeneration. We investigated nerve regeneration by combining a polyglycolic acid collagen (PGA-c) tube, which is approved for clinical use, and Schwann cell-like differentiated ADSCs (dADSCs). METHODS: Fifteen-millimeter-long gaps in the sciatic nerve of rats were bridged in each group using tubes (group I), with tubes injected with dADSCs (group II), or by resected nerve (group III). RESULTS: Axonal outgrowth was greater in group II than in group I. Tibialis anterior muscle weight revealed recovery only in group III. Latency in nerve conduction studies was equivalent in group II and III, but action potential was lower in group II. Transplanted dADSCs maintained Schwann cell marker expression. ATF3 expression level in the dorsal root ganglia was equivalent in groups II and III. DISCUSSION: dADSCs maintained their differentiated state in the tubes and are believed to have contributed to nerve regeneration.

Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of Antibiotics into Pseudomonas aeruginosa Biofilms in Lungs.

Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic-co-glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method. The interactions of the nanoparticles with the biological barriers were comprehensively investigated by using cutting-edge techniques (e.g., quartz crystal microbalance with dissipation monitoring, total internal reflection fluorescence microscopy-based particle tracking, in vitro biofilm model cultured in a flow-chamber system, and quantitative imaging analysis). Our results suggest that the mucus-inert, enzymatically cleavable TPGS shell enables the nanoparticles to penetrate through the mucus, accumulate in the deeper layer of the biofilms, and serve as sustained release depot, thereby improving the killing efficacy of azithromycin (a macrolide antibiotic) against biofilm-forming Pseudomonas aeruginosa. In conclusion, the ultrasmall TPGS-PLGA hybrid nanoparticles represent an efficient delivery system to overcome the multiple barriers and release antibiotics in a sustained manner in the vicinity of the biofilm-forming bacteria.

Clinical outcome after orbital floor fracture reduction with special regard to patient's satisfaction.

PURPOSE: Primary reconstruction via transconjunctival approach is a standardized treatment option for orbital floor fractures. The aim of this study was to compare the findings of specific ophthalmologic assessment with the patient's complaints after fracture reduction. METHODS: A retrospective medical chart analysis was performed on patients who had undergone transconjunctival orbital floor fracture reduction for fracture therapy with resorbable foil (ethisorb sheet or polydioxanone foil). A follow-up assessment including ophthalmological evaluation regarding visual acuity (eye chart projector), binocular visual field screening (Bagolini striated glasses test) and diplopia (cover test, Hess screen test) was conducted. Additionally, a questionnaire was performed to assess patients' satisfaction. RESULTS: A total of 53 patients with a mean follow-up of 23 months (ranging from 11 to 72) after surgical therapy were included. Diplopia was present preoperatively in 23 (43.4%) and reduced in follow-up examination (n = 12, 22.6%). Limitations in ocular motility reduced from 37.7% to 7.5%. The questionnaire about the patient's satisfaction revealed excellent outcomes in relation to the functional and esthetical parameters. CONCLUSION: Transconjunctival approach is a safe approach for orbital fracture therapy. Postoperative diplopia is nearly never perceptible for the individual and differs to pathologic findings in the ophthalmic assessment.

Film-nanoparticle composite for enhanced oral delivery of alpha-casozepine.

Whey-derived alpha-casozepine bioactive peptide (YLGYLEQLLR) was associated with previously optimized guar-gum film-PLGA nanoparticles, aiming to increase both stability across gastrointestinal tract and permeability across absorptive epithelia. Oral films associated with nanoparticles (FNp) enhance buccal absorption along with protection of carried bioactive molecules that are swallowed, with inherent increase of bioavailability. None of developed formulations induced significant loss of cell viability. Permeability across both buccal and intestinal cell barriers was enhanced when alpha-casozepine was carried by FNp system, when compared with film and nanoparticles alone, in a simulated gastrointestinal tract environment. Moreover, differences in permeability profile across buccal and intestinal epithelia were in accordance with the slower erosion of PLGA nanoparticles in a media of neutral pH, resembling oral cavity conditions, and a faster erosion in acidic conditions, as occurs in stomach, as observed by a continuous analysis of nanoparticle morphology over 980 min by atomic force microscopy. Additionally, apparent permeability of alpha-casozepine across TR146 human buccal carcinoma cells and Caco-2/HT29-MTX co-culture, carried by FNp was indeed superior when compared with peptide loaded in PLGA nanoparticles and in films alone or with free peptide control solution. Both FNp and PLGA nanoparticles alone enhanced the permeability of relaxing peptide compared with guar-gum films alone. An increased tongue adhesion when PLGA nanoparticles were added to the guar-gum films was also observed. Developed formulations improved both buccal an intestinal absorption of carried bioactive molecules without compromising cell viability.

Successful treatment of an esophageal perforation that occurred during endoscopic submucosal dissection for esophageal cancer using polyglycolic acid sheets and fibrin glue.

A 74-year-old female, who was diagnosed with superficial esophageal cancer, underwent endoscopic submucosal dissection (ESD) at another hospital, but a perforation occurred during the procedure. The perforation was closed with endoscopic clips, and the ESD was halted. The patient was referred to our hospital, and ESD was retried. There was severe fibrosis around the lesion, and injections into the submucosal layer were difficult. In addition, it was not possible to identify the submucosal layer, and making an oral-side incision caused a large perforation along the incision line. As continuing the submucosal dissection with an endoknife was considered difficult, the lesion was finally resected with hybrid ESD using a snare. The perforation was closed using polyglycolic acid (PGA) sheets and fibrin glue. Endoscopy performed 6 days later showed that the defect had been closed, and no contrast leakage was detected. Follow-up endoscopy conducted 3 months after the ESD showed ulcer healing at the dissection site and scar formation, but no residual tumor or esophageal stricture was noted. Our experience suggests that the use of PGA sheets with fibrin glue is a feasible, safe, and effective way of treating large esophageal perforations during ESD.

Efficacy of triamcinolone-soaked polyglycolic acid sheet plus fully covered metal stent for preventing stricture formation after large esophageal endoscopic submucosal dissection.

Esophageal stricture is a major problem for patients with large superficial esophageal squamous cell neoplasms (SESCNs) after endoscopic submucosal dissection (ESD). Although many measures could be used as prophylaxis for post-ESD strictures, a well-accepted method has not yet been established. We propose using a triamcinolone-soaked polyglycolic acid sheet plus fully covered metal stent (TS-PGA+FCMS) as a novel method to prevent stricture formation after large esophageal ESD. From June 2016 to May 2017, nine patients with SESCNs (≥3/4 of the esophageal circumference) who underwent TS-PGA+FCMS placement immediately after ESD and did not require additional surgical resection were enrolled in this case series. All stents were removed 4-6 weeks post-ESD. The sizes of mucosal defects in 9 patients were 3/4 (n = 1), 4/5 (n = 2), 1/1 (n = 6). The average size of resection was 90.0 mm (range: 60-140 mm). The incidence of stricture was 33.3% (3/9) of patients. No stricture occurred in 3 patients with noncircumferential resection, while stricture occurred in 50% (3/6) patients with circumferential resection. The median number of EBD sessions was 4 (range: 3-4 sessions). No adverse events or recurrences were observed during the median follow-up period of 15.2 months (range: 12-22 months). The TS-PGA+FCMS method is safe and may decrease the incidence of esophageal stricture and the number of EBD sessions after large esophageal ESD.

Oral administration of colitis tissue-accumulating porous nanoparticles for ulcerative colitis therapy.

To improve the penetration and accumulation of anti-inflammatory drugs in colitis tissue, we functionalized the surface of porous poly(lactic-co-glycolic acid) nanoparticles (NPs) using pluronic F127 (PF127) and loaded curcumin (CUR) into the resulting NPs to obtain porous PF127-functionalized CUR-loaded NPs (porous PF127-NPs). These NPs had an average hydrodynamic diameter of about 270 nm with a highly monodisperse size distribution, slightly negative surface charge and controllable CUR release profile. It was found that they had good biocompatibility and yielded a much higher cellular uptake rate of CUR than porous CUR-loaded NPs without PF127 modification (porous NPs). In addition, porous PF127-NPs showed a greater capacity to inhibit the major pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) secreted from lipopolysaccharide-activated macrophages than porous NPs and non-porous PF127-NPs. In vivo experiments suggested that porous PF127-NPs achieved the best therapeutic outcomes against ulcerative colitis (UC) in mice compared with porous NPs and non-porous PF127-NPs. Our results clearly demonstrate that these fabricated porous PF127-NPs show a great promise as an efficient CUR nanocarrier for UC therapy.

Characterization of immunogenicity of avian influenza antigens encapsulated in PLGA nanoparticles following mucosal and subcutaneous delivery in chickens.

Mucosal vaccine delivery systems have paramount importance for the induction of mucosal antibody responses. Two studies were conducted to evaluate immunogenicity of inactivated AIV antigens encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). In the first study, seven groups of specific pathogen free (SPF) layer-type chickens were immunized subcutaneously at 7-days of age with different vaccine formulations followed by booster vaccinations two weeks later. Immune responses were profiled by measuring antibody (Ab) responses in sera and lachrymal secretions of vaccinated chickens. The results indicated that inactivated AIV and CpG ODN co-encapsulated in PLGA NPs (2x NanoAI+CpG) produced higher amounts of hemagglutination inhibiting antibodies compared to a group vaccinated with non-adjuvanted AIV encapsulated in PLGA NPs (NanoAI). The tested adjuvanted NPs-based vaccine (2x NanoAI+CpG) resulted in higher IgG responses in the sera and lachrymal secretions at weeks 3, 4 and 5 post-vaccination when immunized subcutaneously. The incorporation of CpG ODN led to an increase in Ab-mediated responses and was found useful to be included both in the prime and booster vaccinations. In the second study, the ability of chitosan and mannan coated PLGA NPs that encapsulated AIV and CpG ODN was evaluated for inducing antibody responses when delivered via nasal and ocular routes in one-week-old SPF layer-type chickens. These PLGA NPs-based and surface modified formulations induced robust AIV-specific antibody responses in sera and lachrymal secretions. Chitosan coated PLGA NPs resulted in the production of large quantities of lachrymal IgA and IgG compared to mannan coated NPs, which also induced detectable amounts of IgA in addition to the induction of IgG in lachrymal secretions. In both mucosal and subcutaneous vaccination approaches, although NPs delivery enhanced Ab-mediated immunity, one booster vaccination was required to generate significant amount of Abs. These results highlight the potential of NPs-based AIV antigens for promoting the induction of both systemic and mucosal immune responses against respiratory pathogens.

Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin.

Oxytocin is a promising candidate for the treatment of social-deficit disorders such as Autism Spectrum Disorder, but oxytocin cannot readily pass the blood-brain barrier. Moreover, oxytocin requires frequent dosing as it is rapidly metabolized in blood. We fabricated four polymeric nanoparticle formulations using poly(lactic-co-glycolic acid) (PLGA) or bovine serum albumin (BSA) as the base material. In order to target them to the brain, we then conjugated the materials to either transferrin or rabies virus glycoprotein (RVG) as targeting ligands. The formulations were characterized in vitro for size, zeta potential, encapsulation efficiency, and release profiles. All formulations showed slightly negative charges and sizes ranging from 100 to 278 nm in diameter, with RVG-conjugated BSA nanoparticles exhibiting the smallest sizes. No formulation was found to be immunogenic or cytotoxic. The encapsulation efficiency was ≥75% for all nanoparticle formulations. Release studies demonstrated that BSA nanoparticle formulation exhibited a faster initial burst of release compared to PLGA particles, in addition to later sustained release. This initial burst release would be favorable for clinical dosing as therapeutic effects could be quickly established, especially in combination with additional sustained release to maintain the therapeutic effects. Our size and release profile data indicate that RVG-conjugated BSA nanoparticles are the most favorable formulation for brain delivery of oxytocin.

Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite available therapeutic options, the prognosis for patients with GBM remains very poor. We hypothesized that the intra-operative injection of a photopolymerizable hydrogel into the tumor resection cavity could sustain the release of the anti-cancer drug paclitaxel (PTX) encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles and prevent GBM recurrence. The tumor was resected 13 days after implantation and a pre-gel solution composed of polyethylene glycol dimethacrylate (PEG-DMA) polymer, a photoinitiator and PTX-loaded PLGA nanoparticles (PTX PLGA-NPs) was injected into the tumor resection cavity. A solid gel filling the whole cavity was formed immediately by photopolymerization using a 400 nm light. PTX in vitro release study showed a burst release (11%) in the first 8 h and a sustained release of 29% over a week. In vitro, U87 MG cells were sensitive to PTX PLGA-NPs with IC50 level of approximately 0.010 µg/mL. The hydrogel was well-tolerated when implanted in the brain of healthy mice for 2 and 4 months. Administration of PTX PLGA-NPs-loaded hydrogel into the resection cavity of GBM orthotopic model lead to more than 50% long-term survival mice (150 days) compared to the control groups (mean survival time 52 days). This significant delay of recurrence is very promising for the post-resection treatment of GBM.

Nanoparticle mucoadhesive system as a new tool for fish immune system modulation.

Recently, chitosan-based nanoparticles with mucoadhesive properties emerged as a strategy for mucosal drug release. This study aimed to characterize the interaction of mucoadhesive system chitosancoated PLGA nanoparticles (NPMA) with fish external mucus. NP suspensions with fluorescent probe were prepared and characterized by size, polydispersity, zeta potential and pH measures. In post-exposure fish were observed an increase in fluorescence imaging over time and it was significantly influenced by NPMA concentration. We also observed the main predominance the fluorescence in the spleen, followed by liver, gill and other tissues. The use of mucoadhesive nanocarriers becomes an alternative for administration of drugs and immunomodulators in immersion systems since the nanosystem can adhere to the mucosal surface of the fish with little residual effect in the water.

Two-Step Sustained-Release PLGA/Hyaluronic Acid Gel Formulation for Intra-articular Administration.

In the development of drugs for intra-articular administration, sustained-release formulations are desirable because it is difficult to maintain the effect of conventional injections due to immediate drug leakage from the joint cavity. In this study, a sustained-release poly(lactic-co-glycolic acid) (PLGA) microsphere formulation for intra-articular administration containing indocyanine green (ICG) as a model drug was prepared to follow its fate after intra-articular administration in rats with a real-time in-vivo imaging system. ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted outside the body within 1-3 d. However, ICG in the sustained-release formulation was retained in the joint cavity and released for 2 weeks. Next, a sustained-release formulation containing PLGA microspheres in a hyaluronic acid (HA) gel formulation was prepared. After gradual release in two stages, we could achieve sustained release for a longer period. It is considered that a combination formulation of PLGA microspheres and HA gel can significantly improve the sustained release of a drug administered into the knee joint.

In ovo administration of Toll-like receptor ligands encapsulated in PLGA nanoparticles impede tumor development in chickens infected with Marek's disease virus.

One of the economically important diseases in the poultry industry is Marek's disease (MD) which is caused by Marek's disease virus (MDV). The use of current vaccines provides protection against clinical signs of MD in chickens. However, these vaccines do not prevent the transmission of MDV to susceptible hosts, hence they may promote the development of new virulent strains of MDV. This issue persuaded us to explore alternative approaches to control MD in chickens. Induction of innate responses at the early stage of life in the chicken may help to prevent or reduce MDV infection. Further, prophylactic use of Toll-like receptor ligands (TLR-Ls) has been shown to generate host immunity against infectious diseases. In this regard, encapsulation of TLR-Ls in Poly(d, l-lactic-co-glycolic acid) (PLGA) may further enhance host responses by controlled release of TLR-Ls for an extended period. Hence, in the current study, protective effects of encapsulated TLR4 and TLR21 ligands, LPS and CpG, respectively, were investigated against MD. Results indicated that administration of encapsulated CpG and LPS first at embryonic day (ED) 18, followed by post-hatch at 14 days-post infection (dpi) intramuscularly, diminished tumor incidence by 60% and 42.8%, respectively at 21dpi compared to the MDV only group. In addition, analysis of cytokine gene profiles of interferon (IFN)-α, IFN-ß, IFN-γ, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, IL-18 and IL-10 in spleen and bursa of Fabricius at different time points suggests that TLR-Ls possibly triggered host responses through the expression of IL-1ß and IL-18 to reduce tumor formation. However, further studies are needed to explore the role of these pro-inflammatory cytokines and other influencing elements like lymphocytes in the hindrance of tumor development by TLR-Ls treatment in chickens.

Hepatitis B Antigen Loaded Biodegradable Polymeric Nanoparticles: Formulation Optimization and In-vivo Immunization in BALB/c Mice.

OBJECTIVE: The incredibly serious problem of Hepatitis B is virus-related chronic liver disease. The conventional preventive treatment of Hepatitis B requires booster dose, which requires repeated administration of the vaccine to the subject. Thus, there is a need to develop a formulation which can eliminate the need of frequent dosing and enhance patient's acquiescence. To prepare single dose nanovaccine of HBsAg by utilizing central composite design for optimization and interaction of independent variables effects on measured response. METHODS: Nanovaccines were characterized for particle size, morphology, integrity, internalization, proliferation response and haemocompatibility. Nanoparticles at single and multiple doses were compared with booster dose of alum-HBsAg vaccine and measure the immunological marker and cytokine (interleukin-2 and interferon-Y) levels by ELISA techniques in BALB/c mice. RESULTS: The designed nanoparticles were found to have nanometric size, high entrapment efficiency and retained antigen integrity. Nanoparticles showed maximum proliferation and efficiently internalized by lymph and spleen cell without eliciting significant toxicity and haemocampatible. CONCLUSION: The comparable data of anti-HBsAg titre between nanovaccine and alum adsorbed HBsAg demonstrated that single dose of nanoparticles is sufficient for production of immunoglobulin plus cytokine levels, maintain immunogenicity at longer period of time and eliminate the booster dose. Nanovaccines trigger immune responses and showing adjuvant properties.

Nanoparticle-based delivery of carbamazepine: A promising approach for the treatment of refractory epilepsy.

Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.