Search

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1β, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-β1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

Residual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides (ODNs) are double-stranded DNA sequences capable of downregulating the expression of downstream genes of the NF-κB pathway, which is recognized for regulating prototypical proinflammatory signals, physiological bone metabolism, pathologic bone destruction, and bone regeneration. The aim of this study was to investigate the therapeutic effect of NF-κB decoy ODNs on the extraction sockets of Wistar/ST rats when delivered by poly(lactic-co-glycolic acid) (PLGA) nanospheres. Microcomputed tomography and trabecular bone analysis following treatment with NF-κB decoy ODN-loaded PLGA nanospheres (PLGA-NfDs) demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription-quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1β, tumor necrosis factor-α, receptor activator of NF-κB ligand, turnover rate, and increased transforming growth factor-β1 immunopositive reactions and relative gene expression. These data demonstrate that local NF-κB decoy ODN transfection via PLGA-NfD can be used to effectively suppress inflammation in a tooth-extraction socket during the healing process, with the potential to accelerate new bone formation.

Chitosan (CS)-modified poly(D,L-lactide-co-glycolide) (PLGA) nanospheres (NS) were developed and evaluated for use with a nuclear factor kappa B (NF-κB) decoy oligonucleotide (ODN) oral delivery system in an experimental model of ulcerative colitis (UC). Decoy ODN-loaded PLGA NS were prepared by an emulsion solvent diffusion method, and the physicochemical properties of NS were investigated. CS-modified PLGA NS (CS-PLGA NS) showed positive zeta potential, while unmodified PLGA NS (plain-PLGA NS) were negatively charged. Decoy ODN uptake studies with Caco-2 cells using confocal laser scanning microscopy (CLSM) indicated that CS-PLGA NS were more effectively taken up by the cells than plain-PLGA NS. Decoy ODN-loaded CS-PLGA NS were able to improve the stability of ODN against DNase I or an acidic medium, such as gastric juice. Daily oral administration of CS-PLGA NS in a rat model significantly improved dextran sulfate sodium-induced diarrhea, bloody feces, shortening of colon length, and myeloperoxidase activity. Furthermore, decoy ODN-loaded CS-PLGA NS were specifically deposited and adsorbed on the inflamed mucosal tissue of the UC model rat. These results suggested that CS-PLGA NS provide an effective means of colon-specific oral decoy ODN delivery in UC., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Parameters affecting the particle sizes of poly(DL-lactide-co-glycolide) (PLGA) nanospheres produced by the Emulsion Solvent Diffusion (ESD) method were evaluated in this study, so that suitable PLGA nanospheres could be prepared to pass through a membrane filter with 0.2 microm pore size and used as a sterile product. Experimental results demonstrated that the particle sizes of PLGA nanospheres could be reduced by the following efforts. (1) Increase stirring rate of poor solvent. (2) Decrease feed rate of good solvent. (3) Increase poor solvent ratio. (4) Increase the temperature of poor solvent. (5) Decrease polyvinyl alcohol concentration in poor solvent. (6) Increase ethanol concentration in good solvent. (7) Decrease PLGA concentration in good solvent. After optimization, PLGA nanospheres with a mean particle size of 102-163 nm and the 100-98% of filtration fraction could be produced and passed the bacteria challenge tests. This study found PLGA nanospheres can be efficiently prepared as a sterile product.

This paper describes the process of encapsulating hair growing ingredients in the PLGA nanospheres by emulsion solvent diffusion method and investigates the feasibility of using the PLGA nanospheres as the DDS (Drug delivery System) carriers for delivering various hair growing ingredients to hair follicles. In-vitro and in-vivo tests were conducted to verify the performances of encapsulated PLGA nanospheres with three different hair growing ingredients. In the in-vitro tests, the scalp-pore permeability of hair growing ingredient encapsulated PLGA nanospheres (dispersed in the PBS solution) was examined using human scalp biopsies in a modified Bronaugh diffusion chamber in comparison to that of the control samples containing the hair growing ingredient in the PBS solution. Furthermore, the hair growing effect of the encapsulated PLGA nanospheres was evaluated with the C3H mice in the in-vivo tests. By observing the fluorescence intensity of the ingredients, as shown in the cross-section photographs of the human scalp biopsies, it was found that the dispersion liquids containing hair growing ingredient encapsulated PLGA nanospheres exerted a scalp-pore permeability 2.0- to 2.5-fold more marked than that of the control samples. Also, the hair growing activities were enhanced by using the encapsulated PLGA nanospheres, which transformed the hair growth cycle from the resting phase to the growing phase. As a result, the degree of hair growth was improved significantly. These results suggested that the PLGA nanosphere can be a new DDS carrier for delivering hair growing ingredients and drugs to the hair follicles.

Abstract: Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using MechanofusionTM to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the MechanofusionTM technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs. [Copyright &y& Elsevier]