Patient Satisfaction and Patients' Family or Significant Other Perceptions After OnabotulinumtoxinA Treatment: A Prospective Cross-Sectional Study.

BACKGROUND: OnabotulinumtoxinA treatment is associated with improved emotional well-being in patients. OBJECTIVE: This study aimed to determine satisfaction with onabotulinumtoxinA treatment in patients naive to neurotoxin treatment and patients with previous experience with the procedure and evaluate treatment impact on patients' partners, "significant others," or close family members. MATERIALS AND METHODS: Patients' satisfaction and their family's/significant other's perception to treatment outcome were assessed in a prospective, cross-sectional study using standardized questionnaires. RESULTS: OnabotulinumtoxinA treatment was associated with high patient satisfaction ranging from 80% to 100%. Study patients (61 patients) reported that their faces appeared to be more balanced and symmetrical (mean difference, 1.05) and that they looked much better in photographs (mean difference, 1.43), with their significant others also noting the improvement in appearance. Overall, 98% of patients expressed that they would undergo retreatment, and 100% expressed that they would recommend the procedure to others. The main obstacle for treatment repetition was economic constraints (26%). CONCLUSION: OnabotulinumtoxinA treatment is one of the most precise and predictable cosmetic treatments available, with high patient satisfaction (97%). A positive outcome of onabotulinumtoxinA treatment, as expressed by patients surveyed using standardized questionnaires, was the appreciation and acceptance by those in close contact with them.

Pulmonary Administration of Microparticulate Antisense Oligonucleotide (ASO) for the Treatment of Lung Inflammation.

Targeted delivery to the lung for controlling lung inflammation is an area that we have explored in this study. The purpose was to use microparticles containing an antisense oligonucleotide (ASO) to NF-κB to inhibit the production of proinflammatory cytokines. Microparticles were prepared using the B-290 Buchi Spray Dryer using albumin as the microparticle matrix. Physicochemical characterization of the microparticles showed the size ranged from 2 to 5 µm, the charge was - 38.4 mV, and they had a sustained release profile over 72 h. Uptake of FITC-labeled ASO-loaded microparticles versus FITC-labeled ASO solution by RAW264.7 murine macrophage cells was 5-10-fold higher. After pulmonary delivery of microparticles to Sprague-Dawley rats, the microparticles were uniformly distributed throughout the lung and were retained in the lungs until 48 h. Serum cytokine (TNF-α and IL-1ß) levels of rats after induction of lung inflammation by lipopolysaccharide were measured until 72 h. Animals receiving ASO-loaded microparticles were successful in significantly controlling lung inflammation during this period as compared to animals receiving no treatment. This study was successful in proving that microparticulate ASO therapy was capable of controlling lung inflammation.

Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine.

The aim of this study is to develop an orally disintegrating film (ODF) containing a microparticulate measles vaccine formulation for buccal delivery. The measles vaccine microparticles were made with biocompatible and biodegradable bovine serum albumin (BSA) and processed by spray drying. These vaccine microparticles were incorporated in the ODF, consisting of Lycoat RS720®, Neosorb P60W® and Tween 80. The yield of the microparticles was approximately 85-95%, w/w. The mean size of the vaccine microparticles was 3.65 ± 1.89 µm and had a slightly negative surface charge of 32.65 ± 2.4 mV. The vaccine particles were nontoxic to normal cells at high concentrations (500 µg/2.5 × 105 cells) of vaccine particles. There was a significant induction of innate immune response by vaccine microparticles which was observed in vitro when compared to blank microparticles (P < 0.05). The vaccine microparticles also significantly increased the antigen presentation and co-stimulatory molecules expression on antigen presenting cells, which is a prerequisite for Th1 and Th2 immune responses. When the ODF vaccine formulation was dosed in juvenile pigs, significantly higher antibody titers were observed after week 2, with a significant increase at week 4 and plateauing through week 6 comparative to naïve predose titers. The results suggest that the ODF measles vaccine formulation is a viable dosage form alternative to noninvasive immunization that may increase patient compliance and commercial distribution.

Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery.

The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions

Induction of death receptor CD95 and co-stimulatory molecules CD80 and CD86 by meningococcal capsular polysaccharide-loaded vaccine nanoparticles.

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis, and its capsular polysaccharides (CPS) are a major virulence factor in meningococcal infections and form the basis for serogroup designation and protective vaccines. We formulated a novel nanovaccine containing meningococcal CPS as an antigen encapsulated in albumin-based nanoparticles (NPs) that does not require chemical conjugation to a protein carrier. These nanoparticles are taken up by antigen-presenting cells and act as antigen depot by slowly releasing the antigen. In this study, we determined the ability of CPS-loaded vaccine nanoparticles to induce co-stimulatory molecules, namely CD80, CD86, and CD95 that impact effective antigen presentation. Co-stimulatory molecule gene induction and surface expression on macrophages and dendritic cells pulsed with meningococcal CPS-loaded nanoparticles were investigated using gene array and flow cytometry methods. Meningococcal CPS-loaded NP significantly induced the surface protein expression of CD80 and CD86, markers of dendritic cell maturation, in human THP-1 macrophages and in murine dendritic cells DC2.4 in a dose-dependent manner. The massive upregulation was also observed at the gene expression. However, high dose of CPS-loaded NP, but not empty NP, induced the expression of death receptor CD95 (Fas) leading to reduced TNF-α release and reduction in cell viability. The data suggest that high expression of CD95 may lead to death of antigen-presenting cells and consequently suboptimal immune responses to vaccine. The CPS-loaded NP induces the expression of co-stimulatory molecules and acts as antigen depot and can spare antigen dose, highly desirable criteria for vaccine formulations.

Formulation of meningococcal capsular polysaccharide vaccine-loaded microparticles with robust innate immune recognition.

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis associated with a high mortality rate. Capsular polysaccharides (CPSs) are a major virulence factor and form the basis for serogroup designation and protective vaccines. The current polysaccharide meningococcal vaccines are available but are very expensive and require chemical conjugation. Here, we report a novel meningococcal vaccine formulation consisting of meningococcal CPS polymers encapsulated in albumin-based biodegradable microparticles that slowly release antigen and induce robust innate immune responses. Vaccines that elicit innate immunity are reported to have enhanced and protective adaptive immune responses. In this study, the meningococcal CPS-loaded microparticles, but not the empty microparticles, induced the release of IL-8, TNF-α and IL-1ß, enhanced phagocytic capacity and induced robust autophagy in macrophages. The novel meningococcal vaccine microparticles are robustly taken up by macrophages and elicit strong innate immune responses that enhance antigen presentation which is a prerequisite for inducing adaptive immunity.

Implementation of mixture design for formulation of albumin containing enteric-coated spray-dried microparticles.

CONTEXT: Oral delivery of proteins has been a challenging as well as rapidly developing field. OBJECTIVE: To implement mixture design of experiment to develop enteric-coated microparticles containing bovine serum albumin. MATERIALS AND METHODS: Microparticles were prepared using Buchi Spray Dryer 191. Simplex lattice mixture design computed using JMP software was implemented to compare the gastric protection rendered by Eudragit FS30D, Eudragit L100-55, and Eudragit S100 in microparticulate form. Further, an extreme vertices mixture design was used to incorporate hydroxypropyl methylcellulose (HPMC) Chitosan in the formulation to delay the release. Microparticle recovery yield and protein content in microparticles were evaluated. RESULTS AND DISCUSSIONS: The design was statistically significant with Eudragit S100 resulting in protein release of < 5% in acidic buffer. The selected optimal formulation had 70% of Eudragit S, 25% HPMC, and 5% Chitosan. The release profiles of protein from Eudragit S alone and along with HPMC were compared. About 25% decrease in the amount of protein release was observed 6 h post exposure of microparticle to buffer of pH 6.8. The microparticle recovery yield reduced from 77.99% to 71.56% which is due to addition of HPMC into the formulation matrix. CONCLUSION: Although all three Eudragit polymers can be used for enteric coating, in the microparticulate form Eudragit S resulted in higher gastric protection. Also use of HPMC along with Eudragit S resulted in further sustained release.