A Comparison of Self-Esteem Scores for Adolescents Who Have Not Been Pregnant, Have Been Pregnant and Have a Child

The differences in the average self-esteem scores between adolescents who have not been pregnant, adolescents who are pregnant, and adolescents who have a child was the focus of this study. The subjects were adolescents ranging in age from 12 to 19 who were living in a residential treatment facility. The participants were administered the Rosenberg Self-Esteem Inventory. The results found that self-esteem and pregnancy status were weakly correlated but was unable to find a significance due to the low number of subjects

Synthesis of thiolated and acrylated nanoparticles using thiol-ene click chemistry: towards novel mucoadhesive materials for drug delivery

Thiol- and acrylate-functionalized nanoparticles have been synthesized from pentaerythritol tetrakis(3-mercapto-propionate) and pentaerythritol tetraacrylate using thiol-ene click chemistry. Using Raman and 1H NMR spectroscopy as well as Ellman's assay, it was demonstrated that excess pentaerythritol tetraacrylate in the feed mixture led to nanoparticles with free acrylate groups on their surface, whereas nanoparticles with thiolated surfaces could be synthesized using feed mixtures with excess pentaerythritol tetrakis(3-mercapto-propionate). The possibility of fluorescent labelling of thiolated nanoparticles has been demonstrated through their reaction with fluorescein-5-maleimide. The thiolated nanoparticles were found to be mucoadhesive and exhibited retention on mucosal surface of porcine urinary bladder

Methods to determine the interactions of micro- and nanoparticles with mucus

The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. To have a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field

Formulation strategies, preparation methods, and devices for pulmonary delivery of biologics

Biological products, including vaccines, blood components, and recombinant therapeutic proteins, are derived from natural sources such as humans, animals, or microorganisms and are typically produced using advanced biotechnological methods. The success of biologics, particularly monoclonal antibodies, can be attributed to their favorable safety profiles and target specificity. However, their large molecular size presents significant challenges in drug delivery, particularly in overcoming biological barriers. Pulmonary delivery has emerged as a promising route for administering biologics, offering non-invasive delivery with rapid absorption, high systemic bioavailability, and avoidance of first-pass metabolism. This review first details the anatomy and physiological barriers of the respiratory tract and the associated challenges of pulmonary drug delivery (PDD). It further discusses innovations in PDD, the impact of particle size on drug deposition, and the use of secondary particles, such as nanoparticles, to enhance bioavailability and targeting. The review also explains various devices used for PDD, including dry powder inhalers (DPIs) and nebulizers, highlighting their advantages and limitations in delivering biologics. The role of excipients in improving the stability and performance of inhalation products is also addressed. Since dry powders are considered the suitable format for delivering biomolecules, particular emphasis is placed on the excipients used in DPI development. The final section of the article reviews and compares various dry powder manufacturing methods, clarifying their clinical relevance and potential for future applications in the field of inhalable drug formulation

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Background The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy. Methods Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP). Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release characteristics (log DSEDDS/release medium determination) and mucus permeation studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats. Results Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC) increased the effective logP of exenatide from −1.1 to 2.1. SEDDS with a payload of 1% exenatide/DOC had a mean droplet size of 45.87 ± 2.9 nm and a Log DSEDDS/release medium of 1.9 ± 0.05. Permeation experiments revealed 2.7-fold improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in solution. Orally administered exenatide/DOC SEDDS showed a relative bioavailability (versus s.c.) of 14.62% ± 3.07% and caused a significant (p < .05) 20.6% decrease in AUC values of blood glucose levels. Conclusion According to these results, hydrophobic ion pairing in combination with SEDDS represents a promising tool for oral peptide delivery

Novel zwitterionic densely charged neutral sulfobetaine polymeric micelles for oral delivery of therapeutic peptides: a proof-of-concept study

Densely charged but neutral sulfobetaine polymeric micelles (PMs) were designed with the aim of efficiently permeating the intestinal mucus and releasing the intact peptide cargo close to the intestinal epithelial surface. Using RAFT chemistry, butyl methacrylate and dimethyl aminoethyl methacrylate copolymers were synthesised and then reacted with propane sultone to form amphiphilic block copolymers comprising hydrophilic zwitterionic sulfobetaine and lipophilic butyl methacrylate (BMA). Small (diameter <50 nm), spherical BMA–sulfobetaine PMs with a near neutral surface charge potential and loaded with a model peptide cargo, the GLP1-agonist peptide exenatide, were then formed by nanoprecipitation. In vitro peptide release studies from the PMs showed that less than 0.9% of the peptide load was released within the first 2 h (i.e. there was no ‘burst’ effect), with the release unaffected by highly acidic conditions. Thereafter, a sustained release was evident with 43% of the peptide load released in 24 h. In vitro screening (cytotoxicity assay) showed that the PMs did not cause loss of epithelial cell viability. Multiple particle tracking showed that the PMs were very highly permeant through the intestinal mucus. An in vivo non-clinical rodent pharmacokinetic study demonstrated the oral delivery of the exenatide-loaded PMs to achieve an extent of peptide bioavailability of 13% relative to subcutaneous (s.c.) exenatide solution injection. A pharmacodynamic study showed the efficacy of the oral exenatide-loaded PMs with significant reductions in blood glucose following a glucose challenge test. In conclusion, a novel family of sulfobetaine PMs have been demonstrated as stable carriers, efficiently permeating the intestinal mucus and with the potential for exploitation in the oral delivery of therapeutic peptides

Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics

Mucus-Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces

Mucus-penetrating Nanosuspensions, consisting of pure hydrophobic therapeutics with dense muco-inert coatings that enable particles to effectively bypass the mucus barrier, demonstrate superior drug distribution and absorption at mucosal surfaces. With significantly increased drug load compared to polymeric systems and established clinical translation of nanosuspensions-based products, mucus-penetrating nanosuspensions are a promising vehicle for improving mucosal delivery of poorly soluble drugs