A New Analytical Method for Quantifying Acid-End-Cap PLGA in Sub-Milligram Quantities.

Characterization of PLGA polymers used in FDA-approved drug products is critical for quality control and qualitative/quantitative (Q1/Q2) evaluation of potential generic formulations. Various techniques have been developed and used to characterize the molecular properties of PLGA polymers, such as molecular weight, molecular composition, and molecular structure. Commonly used techniques include gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), semisolvent methods, and GPC-based intrinsic viscosity measurement.

In vitro-in vivo correlation (IVIVC) development for long-acting injectable drug products based on poly(lactide-co-glycolide).

In vitro-in vivo correlation (IVIVC), linking in vitro drug release to in vivo drug release or in vivo drug absorption, has been explored chiefly for oral extended-release dosage forms. Currently, there are no official guidelines on IVIVC development for non-oral drug delivery systems. Recently, many long-acting injectable (LAI) formulations based on poly(lactide-co-glycolide) (PLGA) have been developed to deliver various drugs, ranging from small molecules to peptides and proteins, for up to 6 months.

What matters for drug delivery to tumor by nanoparticles: Gaining insights from PBPK/PD simulation of drug nanocrystals.

Background And Purpose: In our previous studies, drug nanocrystals were directly prepared by solution crystallization, possessing uniform particle size and morphology suitable for intravenous (IV) injection. These nanocrystals accumulated in a small percentage of their injected dose in tumor-bearing mice but showed similar anti-tumor effectiveness and much-reduced side effects compared with current commercial solubilized and encapsulated delivery systems.

Experimental Approach: In this study, we aimed to delineate possible controlling factors for the pharmacokinetics (PK) and biodistribution behaviors of paclitaxel (PTX) nanocrystals tested in mice by applying physiologically based pharmacokinetics (PBPK) modeling, coupled with pharmacodynamics (PD) simulation, to the data.

Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution.

Controlled drug delivery technology has matured for more than 70 years, starting from a twice-a-day oral formulation to 6 month long-acting injectable formulations. Further technological advances require superior formulations to treat various diseases more efficiently. Developing future formulations with practical innovations for treating existing and new diseases necessitates our continued efforts to overcome at least three main hurdles.

Treatment efficacy of 532-nm diode laser glottoplasty in patients with sulcus vocalis: a prospective study.

Purpose: This study prospectively assessed the efficacy and safety of 532-nm diode laser glottoplasty in patients with sulcus vocalis.

Methods: A prospective human trial was performed from August 2016 to September 2021. 532-nm diode laser glottoplasty was performed in 30 consecutive patients with sulcus vocalis who suffered from voice problems.

A Novel Intervention That Prevents Vocal Fold Scarring.

Objectives: We evaluated the preventive efficacy of stromal vascular fraction (SVF) for vocal fold scar in a rabbit model.

Study Design: Animal model.

Methods: The study included 40 male New Zealand white rabbits: 20 received vocal fold scar surgery served as normal controls (control group).

The Impact of Post-Processing Temperature on PLGA Microparticle Properties.

Purpose: Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles loaded with either risperidone or naltrexone were prepared from an emulsification homogenization process. The objective of this study was to determine the impact the post-treatment temperature has on the properties and subsequent performance of the microparticles.

Methods: The post-treatment temperature of an ethanolic solution was characterized from 10 ~ 35ºC for the naltrexone and risperidone micropartilces.

Multiphysics Simulation of Local Transport and Absorption Coupled with Pharmacokinetic Modeling of Systemic Exposure of Subcutaneously Injected Drug Solution.

Introduction: Subcutaneous (SC) injectables have become more acceptable and feasible for administration of biologics and small molecules. However, efficient development of these products is limited to costly and time-consuming techniques, partially because absorption mechanisms and kinetics at the local site of injection remain poorly understood.

Objective: To bridge formulation critical quality attributes (CQA) of injectables with local physiological conditions to predict systemic exposure of these products.

Control of drug release kinetics from hot-melt extruded drug-loaded polycaprolactone matrices.

Sustained local delivery of meloxicam by polymeric structures is desirable for preventing subacute inflammation and biofilm formation following tissue incision or injury. Our previous study demonstrated that meloxicam release from hot-melt extruded (HME) poly(ε-caprolactone) (PCL) matrices could be controlled by adjusting the drug content. Increasing drug content accelerated the drug release as the initial drug release generated a pore network to facilitate subsequent drug dissolution and diffusion.

Comparison of humoral and cellular immune responses between ChAd-BNT heterologous vaccination and BNT-BNT homologous vaccination following the third BNT dose: A prospective cohort study.

Introduction: The differential immune responses after two additional BNT162b2 (BNT) booster doses between ChAdOx1 nCoV-10 (ChAd)-primed and BNT-primed groups have not been elucidated. The aim of this study was to compare vaccine-induced humoral and cellular immune responses and evaluate breakthrough infection between the two vaccination strategies.

Methods: In 221 healthy subjects (111 in the ChAd group), longitudinal immune responses were monitored at 3, 4, and 6 months after the 2nd dose and 1, 3, and 6 months after the 3rd dose.

Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil.

In this study, donepezil-loaded PLGA and PLA microspheres (Dp-PLGA-M/Dp-PLA-M) and Dp-PLA-M wrapped in a polyethylene glycol-b-polycaprolactone (PC) hydrogel (Dp-PLA-M/PC) were prepared to reduce the dosing frequency of injections to treat Alzheimer's disease patients. Dp-PLGA-M and Dp-PLA-M with a uniform particle size distribution were repeatably fabricated in nearly quantitative yield and with high encapsulated Dp yields using an ultrasonic atomizer. The injectability and in vitro and in vivo Dp release, biodegradation, and inflammatory response elicited by the Dp-PLGA-M, Dp-PLA-M, and Dp-PLA-M/PC formulations were then compared.

Development of poly(lactide-co-glycolide) microparticles for sustained delivery of meloxicam.

Poly(lactide-co-glycolide) (PLGA) polymers have been widely used for drug delivery due to their biodegradability and biocompatibility. One of the objectives of encapsulating a drug in PLGA microparticles (MPs) is to achieve an extended supply of the drug through sustained release, which can range from weeks to months. Focusing on the applications needing a relatively short-term delivery, we investigated formulation strategies to achieve a drug release from PLGA MPs for two weeks, using meloxicam as a model compound.

Scanning Analysis of Sequential Semisolvent Vapor Impact To Study Naltrexone Release from Poly(lactide-co-glycolide) Microparticles.

Poly(lactide-co-glycolide) (PLGA)-based microparticle formulations have been a mainstay of long-acting injectable drug delivery applications for decades. Despite a long history of use, tools and techniques to analyze and understand these formulations are still under development. Recently, a new characterization method was introduced known as the surface analysis after sequential semisolvent impact using sequential semisolvent vapors.

Challenging the fundamental conjectures in nanoparticle drug delivery for chemotherapy treatment of solid cancers.

Nanomedicines for cancer treatment have been studied extensively over the last few decades. Yet, only five anticancer nanomedicines have received approvals from the United States Food and Drug Administration (FDA) for treating solid tumors. This drastic mismatch between effort and return calls into question the basic understanding of this field.

Implications of particle size on the respective solid-state properties of naltrexone in PLGA microparticles.

A thorough understanding of the complexities in formulating and manufacturing polymeric microspheres is required for new and generic drug applications. Specifically, for an ANDA application for polymeric microsphere-based products, the applicant must meet Q1 (qualitative) and Q2 (quantitative) sameness, and in some cases, Q3 (e.g.

Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly(lactide-co-glycolide) microparticles.

Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase.

Transitioning from a lab-scale PLGA microparticle formulation to pilot-scale manufacturing.

The complexity of scale-up manufacturing of PLGA microparticles creates a significant challenge when transitioning from benchtop-scale formulation development into larger clinical scale batches. Minor changes in the initial formulation composition (e.g.

The First Case Report of Bilateral Vagal Neuropathy Presenting With Dysphonia Following COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a pandemic with a variety of symptoms and complications. Impairments of taste and smell caused by COVID-19 are well known as otolaryngological sequelae. However, dysphonia due to bilateral vagal neuropathy has not been well described as a presenting symptom or complication of COVID-19 infection.

Development of hot-melt extruded drug/polymer matrices for sustained delivery of meloxicam.

For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively.

Evolution of drug delivery systems: From 1950 to 2020 and beyond.

Modern drug delivery technology began in 1952 with the advent of the Spansule® sustained-release capsule technology, which can deliver a drug for 12 h after oral administration through an initial immediate dose followed by the remaining released gradually. Until the 1980s, oral and transdermal formulations providing therapeutic durations up to 24 h for small molecules dominated the drug delivery field and the market. The introduction of Lupron Depot® in 1989 opened the door for long-acting injectables and implantables, extending the drug delivery duration from days to months and occasionally years.

Initial Formation of the Skin Layer of PLGA Microparticles.

Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties have been adjusted to control the drug release kinetics and obtain desirable properties of PLGA-based drug delivery systems. The PLGA microparticle formation begins as soon as the drug/PLGA-dissolved in the organic solvent phase (oil phase) is exposed to the water phase.

Multiscale pharmacokinetic modeling of systemic exposure of subcutaneously injected biotherapeutics.

Subcutaneously injected formulations have been developed for many biological products including monoclonal antibodies (mAbs). A knowledge gap nonetheless remains regarding the absorption and catabolism mechanisms and kinetics of a large molecule at the administration site. A multiscale pharmacokinetic (PK) model was thus developed by coupling multiphysics simulations of subcutaneous (SC) absorption kinetics with whole-body pharmacokinetic (PK) modeling, bridged by consideration of the presystemic clearance by the initial lymph.