Search

The 15-deoxy-(Δ12,14)-PG J(2) (15d-PGJ(2)) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nanotechnological formulation as a carrier for 15d-PGJ(2), and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D,L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ(2). BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 μg/kg 15d-PGJ(2)-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ(2)-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 μg/kg 15d-PGJ(2)-NC had a reduction of CD4(+)CD25(+)FOXP3(+) cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 μg/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 μg/kg 15d-PGJ(2)-NC, and high amounts of 15d-PGJ(2) were observed in the gingiva. In conclusion, the 15d-PGJ(2)-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model.

Aims: To verify whether the nanoencapsulation of 15d-PGJ(2) in poly(D,L-lactide-co-glycolide) (PLGA) nanocapsules (15d-PGJ(2)-NC) might potentialize its antinociceptive activity into rats' temporomandibular joint (TMJ)., Main Methods: Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to evaluate the morphology and suspension of the PLGA nanocapsules. Rats were pretreated (15 min) with an intra-TMJ injection of unloaded 15d-PGJ(2) or 15d-PGJ(2)-NC at concentrations of 10, 100 or 1000 pg followed by an ipsilateral intra-TMJ injection of 1.5% formalin. The nociceptive behavioral response was observed during 45 min; animals were then sacrificed and the periarticular tissue was removed for IL-1β measurements., Key Finding: TEM and AFM analyses showed that 15d-PGJ(2)-NC is spherical without any aggregates or adhesion confirming that this formulation is a good drug carrier system for 15d-PGJ(2). Pretreatment with 15d-PGJ(2)-NC (100 and 1000 pg/TMJ), but not unloaded 15d-PGJ(2), was found to significantly decrease the release of IL-1β cytokine and the animals' nociceptive behavioral response induced by intra-TMJ injection of formalin., Significance: The compound 15d-PGJ(2)-NC might be used as a potential antinociceptive and anti-inflammatory agent to treat temporomandibular disorders in clinical practice., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs)., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: The aim of this work was to investigate the influence of the oily nucleus composition on physico-chemical properties and anesthetic activity of poly (lactide-co-glycolide) nanocapsules with benzocaine., Methods: Nanocapsules containing benzocaine were prepared with three different oily nucleus composition and characterized by mean diameter, polydispersivity, zeta potential, pH and stability were investigated as a function of time. In vitro release kinetics were performed in a system with two compartments separated by a cellulose membrane. Intensity and duration of analgesia were evaluated in rats by sciatic nerve blockade., Results: The greatest stability, slower release profile and improvement in the local anesthetic activity of BZC were obtained with the formulation using USP mineral oil as component., Conclusions: Results from our study provide useful perspectives on selection of the primary materials needed to produce suspensions of polymeric nanocapsules able to act as carriers of BZC, with potential future application in the treatment of pain.

In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency > 87%. These findings open the way for future clinical studies using such formulations.