Microneedle Systems for Vaccine Delivery: the story so far.

INTRODUCTION: Vaccine delivery via a microneedle (MN) system has been identified as a potential alternative to conventional vaccine delivery. MN can be self-administered, is pain-free and is capable of producing superior immunogenicity. Over the last few decades, significant research has been carried out in this area, and this review aims to provide a comprehensive picture on the progress of this delivery platform. AREAS COVERED: This review highlights the potential role of skin as a vaccine delivery route using a microneedle system, examines recent advancements in microneedle fabrication techniques, and provides an update on potential preclinical and clinical studies on vaccine delivery through microneedle systems against various infectious diseases. Articles for the review study were searched electronically in PubMed, Google, Google Scholar, and Science Direct using specific keywords to cover the scope of the article. The advanced search strategy was employed to identify the most relevant articles. EXPERT OPINION: A significant number of MN mediated vaccine candidates have shown promising results in preclinical and clinical trials. The recent emergence of cleanroom free, 3D or additive manufacturing of MN systems and stability, together with the dose-sparing capacity of the Nanopatch® system, have made this platform, commercially, highly lucrative.

Enhancement of solubility and dissolution rate of cryptotanshinone, tanshinone I and tanshinone IIA extracted from Salvia miltiorrhiza.

Cryptotanshinone, tanshinone I and tanshinone IIA are three major components in the extract of Salvia miltiorrhiza with pharmacological significance. However, their effective utilization is limited due to poor water solubility and bioavailability. Solid dispersion (SD) of the extract of Salvia miltiorrhiza was prepared to enhance solubility and dissolution of the three major components. Various carriers were screened for SD preparation by conventional solvent method. Dissolution of the components from selected SD systems was compared with commercial tablets of the extract from Salvia miltiorrhiza. The solubility of three components viz., cryptotanshinone, tanshinone I and tanshinone IIA, after forming SD with either of povidone K-30 (PVP K-30) or poloxamer 407, exhibited enhanced solubility in pH 6.8 buffer. Dissolution test revealed that the amount of three components released was higher from SD tablets as compared to the commercial tablets. Pharmacokinetic profile was evaluated using cryptotanshinone as a representative compound. AUC of cryptotanshinone was significantly increased when administered as a solid dispersion.

Influence of formulation variables in transdermal drug delivery system containing zolmitriptan.

The effects of different formulation variables including pressure sensitive adhesive (PSA), thickness of the matrix, solvent system, inclusion of crystallization inhibitor, loading amount of drug and enhancers on the transdermal absorption of zolmitriptan were investigated. Acrylic adhesive with hydroxyl functional group provided good adhesion force and high flux of zolmitriptan. Pseudopolymorphs of zolmitriptan were found to possess different solid-state properties that affected the permeation rate. Polyoxyethylene alkyl ethers significantly increased the permeation of zolmitriptan through hairless mouse skin. However, these enhancers induced crystallization of zolmitriptan. Kollidon(®) 30 delayed the crystallization without altering the permeation profile of zolmitriptan. Stability studies suggested that terpenes did not induce crystallization of zolmitriptan in the patch and stable formulations could be produced by using cineole and limonene, or their combination.

Recent advances in transdermal drug delivery.

Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, due to the requirements that the patch area should be small enough for the patients to feel comfortable, and to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied. The development of an effective transdermal delivery system is dictated by the unique physicochemical property each drug molecule possesses. In this review, we have summarized various physical and chemical approaches for transdermal flux enhancement, including the application of electricity, ultrasound, microneedle and chemical enhancers. Pressure sensitive adhesive such as acrylics, rubbers and silicones are described together with recent developments. Factors affecting dosage form design, particularly for drug in adhesive system, like adhesion and crystallization are also discussed.

Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy.

In the present study we developed doxorubicin-loaded solid lipid nanoparticles (SLN-Dox) using biocompatible compounds, assessed the in vitro hemolytic effect, and examined their in vivo effects on drug retention and apoptosis intensity in P-glycoprotein-overexpressing MCF-7/ADR cells, a representative Dox-resistant breast cancer cell line. Our SLNs did not show hemolytic activity in human erythrocytes. In comparison with Dox, SLN-Dox efficiently enhanced apoptotic cell death through the higher accumulation of Dox in MCF-7/ADR cells. Therefore, SLN-Dox have potential to serve as a useful therapeutic approach to overcome the chemoresistance of adriamycin-resistant breast cancer. FROM THE CLINICAL EDITOR: Doxorubicin loaded solid lipid nanoparticles (SLN-Dox) were studied in a cell line representative of doxorubicin resistant breast cancer. The nanoparticles did not show hemolytic activity; furthermore, they efficiently enhanced apoptotic cell death through higher accumulation of doxorubicin in cancer cells. This approach may be viable in overcoming the chemoresistance of adriamycin resistant breast cancer.

Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin.

Solid lipid nanoparticles (SLN) loaded with doxorubicin were prepared by solvent emulsification-diffusion method. Glyceryl caprate (Capmul)MCM C10) was used as lipid core, and curdlan as the shell material. Dimethyl sulfoxide (DMSO) was used to dissolve both lipid and drug. Polyethylene glycol 660 hydroxystearate (Solutol)HS15) was employed as surfactant. Major formulation parameters were optimized to obtain high quality nanoparticles. The mean particle size measured by photon correlation spectroscopy (PCS) was 199nm. The entrapment efficiency (EE) and drug loading capacity (DL), determined with fluorescence spectroscopy, were 67.5+/-2.4% and 2.8+/-0.1%, respectively. The drug release behavior was studied by in vitro method. Cell viability assay showed that properties of SLN remain unchanged during the process of freeze-drying. Stability study revealed that lyophilized SLN were equally effective (p<0.05) after 1 year of storage at 4 degrees C. In conclusion, SLN with small particle size, high EE, and relatively high DL for doxorubicin can be obtained by this method.