Experimental design, development and evaluation of extended release subcutaneous thermo-responsive in situ gels for small molecules in drug discovery.

The objective of this work is to develop extended release subcutaneous thermo-responsive in situ gel-forming delivery systems using the following commercially available triblock polymers: poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA, copolymer A & B) and poly (lactide-co-caprolactone)-poly (ethylene glycol)-poly (lactide-co-caprolactone) (PLCL-PEG-PLCL, copolymer C). Performance of two optimized formulations containing ketoprofen as a model compound, was assessed by comparing in vitro drug release profiles with in vivo performance following subcutaneous administration in rats. This work employs a Design of Experiment (DoE) approach to explore first, the relationship between copolymer composition, concentration, and gelation temperature (GT), and second, to identify the optimal copolymer composition and drug loading in the thermo-responsive formulation. Furthermore, this work discusses the disconnect observed between in vitro drug release and in vivo pharmacokinetic (PK) profiles. In vitro, both formulations showed extended-release profiles for 5-9 days, while PK parameters and plasma profiles were similar in vivo without extended release observed. In conclusion, a clear disconnection is observed between in vitro ketoprofen drug release and in vivo performance from the two thermogel formulations tested. This finding highlights a remaining challenge for thermogel formulation development, that is, being able to accurately predict in vivo behavior from in vitro results.

A Beginning Guide for Dental Photography: A Simplified Introduction for Esthetic Dentistry.

Photography is one of the most important skills dentists need to master in order to perform esthetic dentistry at a high level. Today, digital single-lens reflex cameras are commonplace. Young dentists have grown up with Internet, smartphones, and online platforms exposing them, and their patients, to cases that other dentists have shared, increasing the awareness and popularity of esthetic-focused treatment. This article provides readers with a simplified and attainable approach to begin the dental photography journey, as well as increase skill level, depending on practice style and desired investment.

Branding Dynamics for the Esthetic Dentist: Building Your Brand to Build Your Practice.

The objective of this article is to introduce the concept of branding to dentists interested in implementing elective esthetic treatment into their practice. For many, this will serve as an introduction to begin; for others, it can provide a road map for revising and reinforcing a branding program already in place.

A candidate drug administered subcutaneously to rodents as drug particles showing hepatic recirculation which influenced the sustained release process.

The aim of the present study was to evaluate and interpret the pharmacokinetic profiles after subcutaneous (s.c.) administration of crystalline AZ'72 nano- and microsuspensions to rodents. Both formulations were injected at 1.5 and 150 mg/kg to rats. For the lower dose, the profiles were similar after s.c. injection but extended as compared to oral administration. The overall exposure was higher for nanoparticles compared with microparticles during the investigated period. For the higher dose, injection of both suspensions resulted in maintained plateaus caused by the drug depots but, unexpectedly, at similar exposure levels. After addition of a further stabilizer, pluronic F127, nanosuspensions showed improved exposure with dose and higher exposure compared to larger particles in mice. Obviously, a stabilizer mixture that suits one delivery route is not necessarily optimal for another one. The differences in peak concentration (Cmax) between nano- and microparticles were mainly ascribed to differences in dissolution rate. Plasma profiles in mice showed curves with secondary absorption peaks after intravenous and oral administration, suggesting hepatic recirculation following both administration routes. This process, together with the depot formulation, complicates the analysis of absorption from s.c. administration, i.e. multiple processes were driving the plasma profile of AZ'72.

Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet-derived growth factor.

BACKGROUND: Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF interacts extensively with lysophosphatidic acid (LPA). We recently showed that LPA modulates the responses of human gingival fibroblasts to PDGF. The objectives of this study were as follows: 1) to evaluate the basic interactions of LPA with primary human periodontal ligament fibroblasts (PDLFs) alone and with PDGF-BB for promoting PDLF growth and migration; 2) to determine the effects in an in vitro oral wound-healing model; and 3) to identify the LPA receptors (LPARs) expressed by PDLF. METHODS: PDLF regenerative responses were measured using 1 and 10 microM LPA in the absence or presence of 1 or 10 ng/ml PDGF. Cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and by cell counting. Migration responses were measured using a microchemotaxis chamber. PDLFs were grown to confluence on glass slides, a 3-mm-wide wound was mechanically inflicted, and wound fill on days 4, 6, and 9 was reported. PDLF LPAR expression was determined using Western blotting. RESULTS: PDLFs exhibited proliferative and chemotactic responses to LPA; these responses were enhanced when LPA and PDGF were present together. LPA plus PDGF elicited complete wound fill. PDLFs express the LPARs LPA(1), LPA(2), and LPA(3). CONCLUSIONS: To our knowledge, this study provides the first evidence that LPA stimulates human PDLF wound healing responses and interacts positively with PDGF to regulate these actions. These results suggest that LPA and its receptors play important modulatory roles in PDLF regenerative biology.