Experimental design and optimization of a novel dual-release drug delivery system with therapeutic potential against infection with Helicobacter pylori.

The objective of this study was to develop clarithromycin-loaded lipid nanocarriers and incorporate them into microcapsules for pH-specific localized release of clarithromycin in the Helicobacter pylori microenvironment in order to obtain a gastro-retentive and pH-sensitive formulation. A Plackett-Burman design was applied to identify the effect of 5 factors on 3 responses. Then, a central composite design was applied to estimate the most important factors leading to the best compromise between lower particle size, polydispersity index and particle size changes. The optimized clarithromycin-loaded nanocapsules were employed to generate microcapsules by different methodologies. Nanocarriers and microcapsules were characterized in vitro. Experimental design and conditions were optimized to obtain nanocapsules of around 100 nm by a modified phase inversion-based process. High particle size homogeneity and high stability were achieved. At 4 °C both optimized lipid nanocapsules were stable during at least 365 days, confirming stability under those conditions. Clarithromycin incorporation in the nanocarrier was effective. Both types of microcoating were evaluated regarding their pH sensitivity. Spray drying microcapsules exhibited similar and uncontrolled release profiles at pH 2 and 7.4. Alternatively, when microcoatings were generated using an Encapsulator, release was insignificant at pH 2, while at pH 7.4 release was triggered, and appeared more appropriate to formulate microcapsules that release nanocarriers under pH neutral Helicobacter pylori microenvironment conditions, thereby permitting effective drug delivery in infected locations. The release of clarithromycin from lipid nanocarrier loaded microcapsules was pH-sensitive suggesting that this could be an effective strategy for clarithromycin delivery to the Helicobacter pylori microenvironment. Clarithromycin nanocapsules with and without microcoating showed a high anti-Helicobacter pylori activity in vitro.

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems.

Currently, most vaccines available on the market are for parental use; however, this may not be the best option on several occasions. Mucosal routes of administration such as intranasal, sublingual, and buccal generate great interest due to the benefits they offer. These range from increasing patient compliance to inducing a more effective immune response than that achieved through conventional routes. Due to the activation of the common mucosal immune system, it is possible to generate an effective systemic and local immune response, which is not achieved through parenteral administration. Protection against pathogens that use mucosal entry routes is provided by an effective induction of mucosal immunity. Mucosal delivery systems are being developed, such as films and microneedles, which have proven to be effective, safe, and easy to administer. These systems have multiple advantages over commonly used injections, which are simple to manufacture, stable at room temperature, painless for the patient since they do not require puncture. Therefore, these delivery systems do not require to be administered by medical personnel; in fact, they could be self-administered.