The Relationship between the Drug Delivery Properties of a Formulation of Teriparatide Microneedles and the Pharmacokinetic Evaluation of Teriparatide Administration in Rats.

PURPOSE: Teriparatide is an effective drug for the treatment of osteoporosis. This study examines the relationship between the drug delivery properties of the solid formulation with teriparatide and the pharmacokinetic properties of teriparatide in vivo. METHODS: Teriparatide microneedles with different dissolution rates were prepared using sucrose and carboxymethylcellulose (CMC). There were three aspects of this study: (1) The dissolution rate of teriparatide from both formulations (sucrose and CMC) was measured in vitro. (2) After administration into porcine skin ex vivo, the diffusion rate of FITC-dextran was observed using a confocal microscope. (3) Pharmacokinetic studies were performed in rats and pharmacokinetic data compared with the release rate and the diffusion pattern. RESULTS: In the in vitro dissolution experiment, 80% of teriparatide was released within 30 min from the CMC MNs, whereas 80% of teriparatide was released within 10 min from the sucrose MNs. After 30 min, the fluorescence intensity on the surface of the MNs was 40% of the initial intensity for sucrose MNs and 90% for CMC MNs. In the pharmacokinetic study, the Cmax values of the CMC and sucrose MNs were 868 pg/mL and 6809 pg/mL, respectively, and the AUClast values were 6771 pg*hr/mL for the CMC MNs and 17,171 pg*hr/mL for the sucrose MNs. CONCLUSIONS: When teriparatide is delivered into the skin using microneedles, the release rate from the solid formulation determines the drug's pharmacokinetic properties. The diffusion pattern of fluorescence into the skin can be used to anticipate the pharmacokinetic properties of the drug.

Formulation And Evaluation Of Nanostructured Lipid Carriers (NLCs) Of 20(S)-Protopanaxadiol (PPD) By Box-Behnken Design.

BACKGROUND: 20(S)-Protopanaxadiol (PPD) has a higher anti-wrinkle effect than the other glycone forms of ginsenosides. However, as PPD has low solubility in water and a high molecular weight, it cannot easily penetrate the stratum corneum layer, which is the rate-limiting step of topical skin delivery. Thus, the objective was to enhance the topical skin deposition of PPD using an optimized nanostructured lipid carriers (NLC) formulation. NLC formulations were optimized using a Box-Behnken design. MATERIALS AND METHODS: NLC formulations were optimized using a Box-Behnken design, where the amount of PDD (X1), volume of the liquid lipid (X2), and amount of surfactant (X3) were set as the independent variables, while the particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) were dependent factors. An in vitro deposition study was performed using Strat-M® and human cadaver skin, while in vivo skin irritation effect of the NLC formulation was evaluated in humans. RESULTS: An NLC was successfully prepared based on the optimized formulation determined using the Box-Behnken design. The particle size, PDI, and EE of the NLC showed less than 5% difference from the predicted values. The in vitro deposition of PPD after the application of the NLC formulation on a Strat-M® artificial membrane and human cadaver skin was significantly higher than that of the controls. Moreover, NLC formulations with and without PDD were not skin irritants in a human study. CONCLUSION: An NLC formulation for the topical delivery of PPD was successfully optimized using the Box-Behnken design, and could be further developed to enhance the topical skin deposition of PPD.

Curcumin-loaded lipid-hybridized cellulose nanofiber film ameliorates imiquimod-induced psoriasis-like dermatitis in mice.

Cellulose nanofiber (CNF) is an attractive biomaterial given its film-forming properties, excellent mechanical properties and biocompatibility. Herein, CNF film was prepared as a topical drug delivery system by hybridizing curcumin (Cur)-loaded nanostructured lipid carriers (NLCs). NLCs with a mean diameter of ≈500 nm were fabricated by using a solvent diffusion method. The lipid composition of the NLCs was optimized based on the efficiency of Cur delivery to the artificial skin and mechanical strength of the developed films, where a composition containing shea butter and Capmul MCM EP exhibited the highest values of 233.2 ±â€¯96.6 µg/cm2/mg and 4.86 ±â€¯0.14 MPa, respectively. The Cur-loaded lipid-hybridized CNF (lipid@CNF) films with a smooth rather than particle-embedded surface were obtained by vacuum filtration of the NLCs and CNF mixture, which were confirmed by TEM, SEM, AFM, XPS, and FTIR analyses. The Cur-loaded lipid@CNF films exhibited more than 2.0-fold increases in Cur deposition to the epidermis of imiquimod (IMQ)-induced psoriatic mouse compared with the films without lipids, which potentially resulted from the amorphous state of Cur observed in the DSC and PXRD analyses and the permeation-enhancing effect of lipids. The in vivo anti-psoriatic efficacy test revealed that the Cur-loaded lipid@CNF films ameliorated the psoriatic skin symptoms in IMQ-induced mice, reducing the pro-inflammatory cytokine levels in the skin almost comparable to a commercially available topical corticosteroid cream. These results could be attributed to the enhanced Cur deposition along with the skin hydration effect of the films. These findings suggest that the developed CNF films can be used as a promising topical drug delivery system for psoriasis therapy.