Abstract. In the current study, novel paclitaxel-loaded cross-linked hyaluronan nanoparticles were engineered for the local delivery of paclitaxel as a prototype drug for cancer therapy. The nanoparticles were prepared using a desolvation method with polymer cross-linking. In vitro cytotoxicity studies demonstrated that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free paclitaxel, regardless of the dose. These results suggest that hyaluronan nanoparticles maintain the pharmacological activity of paclitaxel and efficiently deliver it to the cells. Furthermore, in vivo administration of the drug-loaded nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded nanoparticles treated group showed effective inhibition of tumor growth in all treated rats. Interestingly, there was one case of complete remission of tumor nodule and two cases of persistent reduction of tumor size that was observed on subsequent days. In the case of free paclitaxel-treated group, the mean tumor volume increased almost linearly (R 2 =0.93) with time to a size that was 4.9-fold larger than the baseline volume at 57 days post-drug administration. Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could be a promising treatment modality for solid mammary tumors.

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The aim of this study was to investigate olanzapine (OZ) systemic absolute bioavailability after intranasal (i.n.) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of olanzapine following intranasal administration. Olanzapine-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions and studied in terms of their size, drug loading, and in vitro release. The OZ nanoparticles were administered i.n. to rabbits, and OZ plasma concentration at predetermined time points was compared to i.n. administration of OZ in solution. The concentrations of OZ in plasma were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). OZ-loaded chitosan nanoparticles significantly (p < 0.05) enhanced systemic absorption with 51 ± 11.2% absolute bioavailability as compared to 28 ± 6.7% after i.n. administration of OZ solution. The results of the present study suggest that intranasal administration of OZ-loaded chitosan nanoparticles formulation could be an attractive modality for delivery of OZ systemically.

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The purpose of this study was to develop a sublingual spray drug delivery formulation of oxycodone and evaluate the effect of formulation pH on sublingual absorption of oxycodone for acute pain management using rabbit as the animal model. Using a new, sensitive, and specific liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization detector assay, the absorption bioavailability of sublingual oxycodone was determined in rabbits by comparing plasma concentration after sublingual spray delivery with equivalent intravenous dose. The effect of formulation pH on sublingual absorption of oxycodone was also tested on rabbits that had received oxycodone sublingually at a dose of 0.1 mg/0.1 mL (pH 4.0 and 9.0). Blood samples were collected at different time points, and plasma oxycodone concentrations were determined by LC/MS. Following administration of a 0.1 mg dose, the average C(max) values were found to be 64.9 +/- 12.1 and 95.2 +/- 10.1 ng/mL, for pH 4.0 and 9.0, respectively. The area under the curve (AUC) values were found to be 5807.0, and 8965.3 ng.min/mL for formulation pH 4.0 and 9.0, respectively. The mean sublingual bioavailability of oxycodone was 45.4% +/- 20.1% and 70.1% +/- 17.9%, for pH 4.0 and 9.0, respectively. The formulation pH had no significant influence on oxycodone bioavailability (P < .05). A sublingual spray dosage form of oxycodone hydrochloride would be a good alternative for fast onset pain management, especially in children.