Evaluating the Release of Different Commercial Orally Modified Niacin Formulations In Vitro.

OBJECTIVES: To evaluate the release profile of different modified-release oral formulations of niacin, such as immediate-release (IR) powder and tablets, timed-release (TR) caplets, extended-release (ER) capsules, and controlled-release (CR) tablets, to assure their defined release pattern and correlate this release with their matrix polymers. SIGNIFICANCE: Niacin is used to manage hyperlipidemia by reducing cutaneous flushing and hepatotoxicity adverse events. The release profiles of different types of modified-release dosage forms depend on the types of coating materials (polymers) used in the matrix formation. Although different types of niacin formulations exist, none of the niacin dissolution profiles have been evaluated and compared in the literature. METHODS: Four commercial orally modified-release niacin brands were collected from a local CVS pharmacy retail store, in Miami, FL, USA. The in vitro release study was conducted in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) conditions. RESULTS: The results of the release patterns of four niacin-modified dosage forms (IR, ER, TR, and CR) were aligned with their release definitions. However, the CR dosage form did not follow an ideal release pattern. CONCLUSIONS: The release rate of niacin in vitro was pH dependent, which was confirmed by the similarity factor (f2) results. All the f2 comparison values were below 50 in both the SIF and SGF media, while all the comparisons were below the f2 values for all brands in the SIF media.

The Autoinducer N-Octanoyl-L-Homoserine Lactone (C8-HSL) as a Potential Adjuvant in Vaccine Formulations.

Autoinducers AI-1 and AI-2 play an important role in bacterial quorum sensing (QS), a form of chemical communication between bacteria. The autoinducer N-octanoyl-L-Homoserinehomoserine lactone (C8-HSL) serves as a major inter- and intraspecies communicator or 'signal', mainly for Gram-negative bacteria. C8-HSL is proposed to have immunogenic properties. The aim of this project is to evaluate C8-HSL as a potential vaccine adjuvant. For this purpose, a microparticulate formulation was developed. The C8-HSL microparticles (MPs) were formulated by a water/oil/water (W/O/W) double-emulsion solvent evaporation method using PLGA (poly (lactic-co-glycolic acid)) polymer. We tested C8-HSL MPs with two spray-dried bovine serum albumin (BSA)-encapsulated bacterial antigens: colonization factor antigen I (CFA/I) from Escherichia coli (E. coli.) and the inactive protective antigen (PA) from Bacillus anthracis (B. anthracis). We formulated and tested C8-HSL MP to determine its immunogenicity potential and its ability to serve as an adjuvant with particulate vaccine formulations. An in vitro immunogenicity assessment was performed using Griess's assay, which indirectly measures the nitric oxide radical (NOˑ) released by dendritic cells (DCs). The C8-HSL MP adjuvant was compared with FDA-approved adjuvants to determine its immunogenicity potential. C8-HSL MP was combined with particulate vaccines for measles, Zika and the marketed influenza vaccine. The cytotoxicity study showed that MPs were non-cytotoxic toward DCs. Griess's assay showed a comparable release of NOˑ from DCs when exposed to CFA and PA bacterial antigens. Nitric oxide radical (NOˑ) release was significantly higher when C8-HSL MPs were combined with particulate vaccines for measles and Zika. C8-HSL MPs showed immunostimulatory potential when combined with the influenza vaccine. The results showed that C8-HSL MPs were as immunogenic as FDA-approved adjuvants such as alum, MF59, and CpG. This proof-of-concept study showed that C8-HSL MP displayed adjuvant potential when combined with several particulate vaccines, indicating that C8-HSL MPs can increase the immunogenicity of both bacterial and viral vaccines.

Potential Applications of Microparticulate-Based Bacterial Outer Membrane Vesicles (OMVs) Vaccine Platform for Sexually Transmitted Diseases (STDs): Gonorrhea, Chlamydia, and Syphilis.

Sexually transmitted diseases (STDs) are a major global health issue. Approximately 250 million new cases of STDs occur each year globally. Currently, only three STDs (human papillomavirus (HPV), hepatitis A, and hepatitis B) are preventable by vaccines. Vaccines for other STDs, including gonorrhea, chlamydia, and syphilis, await successful development. Currently, all of these STDs are treated with antibiotics. However, the efficacy of antibiotics is facing growing challenge due to the emergence of bacterial resistance. Therefore, alternative therapeutic approaches, including the development of vaccines against these STDs, should be explored to tackle this important global public health issue. Mass vaccination could be more efficient in reducing the spread of these highly contagious diseases. Bacterial outer membrane vesicle (OMV) is a potential antigen used to prevent STDs. OMVs are released spontaneously during growth by many Gram-negative bacteria. They present a wide range of surface antigens in native conformation that possess interesting properties such as immunogenicity, adjuvant potential, and the ability to be taken up by immune cells, all of which make them an attractive target for application as vaccines against pathogenic bacteria. The major challenge associated with the use of OMVs is its fragile structure and stability. However, a particulate form of the vaccine could be a suitable delivery system that can protect the antigen from degradation by a harsh acidic or enzymatic environment. The particulate form of the vaccine can also act as an adjuvant by itself. This review will highlight some practical methods for formulating microparticulate OMV-based vaccines for STDs.

A Review on Current COVID-19 Vaccines and Evaluation of Particulate Vaccine Delivery Systems.

First detected in Wuhan, China, a highly contagious coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19, spread globally in December of 2019. As of 19 September 2021, approximately 4.5 million people have died globally, and 215 million active cases have been reported. To date, six vaccines have been developed and approved for human use. However, current production and supply capabilities are unable to meet global demands to immunize the entire world population. Only a few countries have been able to successfully vaccinate many of their residents. Therefore, an alternative vaccine that can be prepared in an easy and cost-effective manner is urgently needed. A vaccine that could be prepared in this manner, as well as can be preserved and transported at room temperature, would be of great benefit to public health. It is possible to develop such an alternative vaccine by using nano- or microparticle platforms. These platforms address most of the existing vaccine limitations as they are stable at room temperature, are inexpensive to produce and distribute, can be administered orally, and do not require cold chain storage for transportation or preservation. Particulate vaccines can be administered as either oral solutions or in sublingual or buccal film dosage forms. Besides improved patient compliance, the major advantage of oral, sublingual, and buccal routes of administration is that they can elicit mucosal immunity. Mucosal immunity, along with systemic immunity, can be a strong defense against SARS-CoV-2 as the virus enters the system through inhalation or saliva. This review discusses the possibility to produce a particulate COVID vaccine by using nano- or microparticles as platforms for oral administration or in sublingual or buccal film dosage forms in order to accelerate global vaccination.