Polymeric Systems as Nanodevices for siRNA Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dioctadecyldimethylammonium:Monoolein Nanocarriers for Efficient in Vitro Gene Silencing

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss

p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.

Drug delivery systems: Past, present, and future

Drug delivery systems are essential components of drugs controlled release. In the last decades, several drug delivery technologies have emerged including capsules, liposomes. microparticles, nanoparticles, and polymers. These components must be biocompatible, biodegradable, and display a desired biodistribution providing a long-term availability of the therapeutic at specific target over time.

Colloidal carriers for ophthalmic drug delivery

To achieve effective drug concentration at the intended site for a sufficient period of time is a requisite desired for many drug formulations. For drugs intended to ocular delivery, its poor bioavailability is due to pre-corneal factors. Most ocular diseases are treated by topical drug application in the form of solution, suspension and ointment. However, such dosage forms are no longer sufficient to combat some ocular diseases. Intravitreal drug injection is the current therapy for disorders in posterior segment. The procedure is associated with a high risk of complications, particularly when frequent, repeated injections are required. Thus, sustained-release technologies are being proposed, and the benefits of using colloidal carriers in intravitreal injections are currently under investigation for posterior drug delivery. This review will discuss recent progress and specific development issues relating to colloidal drug delivery systems, such as liposomes, niosomes, nanoparticles, and microemulsions in ocular drug delivery.

Subconjunctival Delivery of Antibiotics in a Controlled-Release System A Novel Anti-infective Prophylaxis Approach for Cataract Surgery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nanotechnology-based Drug Delivery Systems for Dermatomycosis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rheological, Mechanical and Adhesive Properties of Surfactant-Containing Systems Designed as a Potential Platform for Topical Drug Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Xylan from corn cobs, a promising polymer for drug delivery: Production and characterization

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 2: Physical parameters, cross-linking degrees and drug delivery relationships

High amylose cross-linked to different degrees with sodium trimetaphosphate by varying base strength (2% or 4%) and contact time (0.5-4 h) was evaluated as non-compacted systems for sodium diclophenac controlled release. The physical properties and the performance of these products for sodium diclophenac controlled release from non-compacted systems were related to the structures generated at each cross-linking degree. For samples at 2% until 2 h the swelling ability, G' and eta* values increased with the cross-linking degree, because the longer polymer chains became progressively more entangled and linked. This increases water uptake and holding, favoring the swelling and resulting in systems with higher viscosities. Additionally, the increase of cross-linking degree should contribute for a more elastic structure. The shorter chains with more inter-linkages formed at higher cross-linking degrees (2%4h and 4%) make water caption and holding difficult, decreasing the swelling, viscosity and elasticity. For 2% samples, the longer drug release time exhibited for 2%4h sample indicates that the increase of swelling and viscosity contribute for a more sustained drug release, but the mesh size of the polymeric network seems to be determinant for the attachment of drug molecules. For the 4% samples, smaller meshes size should determine less sustained release of drug. (C) 2008 Elsevier B.V. All rights reserved.

Mucoadhesive drug delivery systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Intranasal delivery of zidovudine by PLA and PLA-PEG blend nanoparticles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro characterization of coevaporates containing chitosan for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Chitosan-pectin multiparticulate systems associated with enteric polymers for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis

Importance of the field: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Area covered in this review: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.What the reader will gain: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.Take home message: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.