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Mucoadhesive buccal films (MBFs) become the most promising buccal mucosal delivery system duo to its advantageous properties, including simple preparation technique and better patient compliance. The mechanical properties and mucoadhesion of MBFs are crucial in their successful performance as well as manufacturing and administration. In this study, we prepared hollow mesoporous silica nanoparticles-loaded ion-crosslinked bilayer films (CCS-PVA-TPP-FSM@HMSNs) using carboxymethyl chitosan (CCS) and polyvinyl alcohol (PVA) for buccal delivery of furosemide (FSM). The FSM-loaded hollow mesoporous silica nanoparticles (FSM@HMSNs) were firstly characterized by SEM, TEM, and nitrogen adsorption/desorption. Then, we constructed an ion-crosslinked network using CCS and PVA employed with the solution casting method, and sodium tripolyphosphate (TPP) was used as a hydrogen bond crosslinking agent. The formulation was optimized through Box-Behnken design, where the impact of the proportion of the ingredients on the quality of the films was evaluated entirely. Herein, folding endurance, swelling, tensile strength, and adhesion force were selected as response variables. Morphology, mechanical, spectroscopic, thermal, and safety of CCS-PVA-TPP-FSM@HMSNs films were also investigated. The release and permeability behaviors of CCS-PVA-TPP-FSM@HMSNs films were evaluated by in vitro drug release, across isolated porcine buccal and TR146 cell model. The CCS-PVA-TPP-FSM@HMSNs films showed outstanding mechanical properties, suitable bioadhesion, high drug loading, significant sustained-release properties, and improved permeability. In pharmacokinetic study with golden hamster models, the relative bioavailability was increased by 191.54%, and the absolute bioavailability was 82.20%. In summary, this study provides evidence that this innovative CCS-PVA-TPP-FSM@HMSNs films could be a promising and industrialized buccal drug delivery system.

For the development of in-situ gelling and mucoadhesive acetaminophen liquid suppository prepared with poloxamers (P 407, P 188) and sodium alginate, the physicochemical characteristics of liquid suppositories [acetaminophen/P 407/P 188/sodium alginate (5/15/19/0–1.0%)] were evaluated. Furthermore, a pharmacokinetic study of acetaminophen from liquid and conventional solid suppositories in human subjects was carried out. The results showed that acetaminophen liquid suppository [acetaminophen/P 407/P 188/sodium alginate (5/15/19/0.6%)] with optimal gelation temperature, gel strength and bioadhesive force had a similar release pattern to conventional suppository. The area under the drug concentration–time curve (AUC), mean residence time (MRT), biological half-life (t1/2) and apparent elimination rate constant (Kel) of acetaminophen from liquid suppository were not significantly different from those from conventional suppository. However, liquid suppository gave significantly faster the time to reach the maximum plasma concentration (Tmax) and higher the maximum plasma concentration of drug (Cmax) of acetaminophen than conventional suppository (p

The purpose of this study was to improve the solubility and enhance the bioavailability of poorly water-soluble cyclosporin A loaded in o/w microemulsion systems. Microemulsions with varying weight ratios of surfactant to cosurfactant were prepared using caprylic/capric triglyceride (Captex 355®) as an oil, polyoxyethylated castor oil (Cremophor EL®) as a surfactant, Transcutol® as a cosurfactant and saline. The area of o/w microemulsion region in pseudo-ternary phase diagram was increased with increasing ratio of Cremophor EL® to Trancutol®. The solubility of cyclosporin A in microemulsion systems reached the maximum with 2:1 mixture of Cremophor EL® and Trancutol®. The dispersion rate of oil–surfactant–cosurfactant mixture with varying ratios of Cremophor EL® to Trancutol® in aqueous media assuming the condition of gastric fluid decreased with the increase of Cremophor EL® to Trancutol® weight ratio. The droplet size of microemulsion without cyclosporin A was decreased with the increase of Cremophor EL® content. The droplet size increased on increasing the incorporation of cyclosporin A. The droplet size of cyclosporin A loaded microemulsion was minimized with microemulsions prepared with 2:1 mixture of surfactant to cosurfactant (Cremophor EL®:Transcutol®:Captex 355®, 10:5:4). The maximal blood concentration (Cmax) of cyclosporin A and the area under the drug concentration-time curve (AUC) after oral administration of this cyclosporin A loaded microemulsion was 3.5 and 3.3 fold increased compared with Sandimmun®. No significant difference of Cmax and AUC was observed between this microemulsion system and Sandimmun Neoral®. The absolute bioavailability of cyclosporin A loaded in this microemulsion system was increased about 3.3 and 1.25 fold compared with Sandimmun® and Sandimmun Neoral®. The enhanced bioavailability of cyclosporin A loaded in this microemulsion system might be due to the reduced droplet size of microemulsion systems.

Non-viral gene delivery carriers were prepared by using DNA/polyethylenimine/polymethacrylic acid (DPP) polyplexes and its extravasation from tumor blood vessel was evaluated with mouse dorsal skin fold window chamber model. The DNA/PEI (DP) complex with a ratio of N to P (10/1) was coated with polymethacrylic acid, and the ratio of PMA to DNA complex in DNA/PEI/PMA (DPP) polyplex was fixed 0.03 (w/w). The surface charges of the DP and DPP polyplex were positive 26 and 15, respectively. The size of DP and DPP polyplex were 161 nm and 195 nm. The transfection efficiencies in HepG2 cells were about 30-fold and 20-fold higher than that in HeLa and L/C cells in the presence of 50% serum, respectively. The DPP polyplex showed a reduced erythrocyte aggregation activity and a decreased cytotoxicity in cancer cells. After being incubated 30 min, Fluorescently labelled DPP polyplex uptaken by cancer cells decreased, compared with DP by measuring flowcytometry. DPP polyplex penetrating through tumor blood vessel appeared fast and stayed longer in tumour interstitial, this fact was observed from mouse dorsal skin fold window chamber model.

The purpose of the present study is to prepare chemically and physically stable rhEGF/poloxamer gel and to investigate its possibility of ophthalmic delivery. The rhEGF/HP-beta-CD complex markedly increased rhEGF stability compared with rhEGF solution at 4 degrees C. The poloxamer gel was composed of poloxamer 407 (16%) and poloxamer 188 (14%). Additive of rhEGF/HP-beta-CD complexes increased the gelation temperature and 0.5% rhEGF/HP-beta-CD complex exhibited a suitable gelation temperature (35.5 degrees C). The gel strength and bioadhesive force decreased by increasing the rhEGF and HP-beta-CD ratio from 1:4 to 1:20 in the complex. The in vitro release of rhEGF from poloxamer gel containing 1:4 rhEGF/HP-beta-CD complex was much slower than that of rhEGF solution and faster than that of 1:20 rhEGF/HP-beta-CD complex. After ocular administration of poloxamer gels in the rabbit, the concentration of rhEGF in tear declined at a first-order elimination. The poloxamer gel containing rhEGF/HP-beta-CD complex increased the area under the concentration-time curve (AUC) of rhEGF in tear fluid compared with gel containing rhEGF solution. 1:20 ratio of rhEGF/HP-beta-CD exhibited high AUC, indicating that rhEGF may be retained in the pre-corneal area for prolonged period. Therefore, the poloxamer gel could be applicable for the development of effective ophthalmic delivery.