The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2(3) factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320-498 nm, and the EE was between 32.89 and 56.56 %. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery.

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In the present study, tramadol HCl microspheres were designed in order to accomplish rapid delivery of drug to the brain. For this purpose, lower viscosity grade HPMC (E15) was chosen as mucoadhesive polymer and used at different drug/polymer ratios in the microspheres formulations. The spray-dried microspheres were evaluated with respect to the production yield, incorporation efficiency, particle size, mucoadhesive property, in vitro drug release, histopathological study, and radio imaging study in rabbits. DSC and XRD study showed molecular dispersion and conversion of the drug into amorphous form. Size and surface morphology of microspheres was analyzed by SEM and found to be spherical in shape with smooth surface. It was found that the particle size, swelling ability, and incorporation efficiency of microspheres increase with increasing drug-to-polymer ratio. Microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. In vitro drug release of optimized formulation was found to be 94% after 90 min. The radio imaging study indicated localization of drug in the brain. Hence, tramadol HCl microspheres based on a HPMC E15 may be a promising nasal delivery system for CNS targeting.

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Objectives: Dentofacial orthopaedic treatment of mandibular hypoplasia has unpredictable skeletal outcomes. Although several biomodulators including insulin-like growth factor 1 (IGF-1) are known to contribute to chondrocyte proliferation, their efficacy in modulating mandibular growth has not been validated. The aim of this study was to determine the effect of locally delivered IGF-1 on mandibular growth and condylar bone quality/quantity in juvenile rats.