Compatibility of PEGylated Polymer Nanoparticles with the Biophysical Function of Lung Surfactant

To minimize an unwanted interference of colloidal drug delivery vehicles with the biophysical functionality of lung surfactant, the surface of polymer nanoparticles was modified with poly­(ethylene glycol) (PEGylation). Plain poly­(lactide) nanoparticles provoked a statistically relevant decrease in the surface activity of the naturally derived lung surfactant, Alveofact. By contrast, the extent of lung surfactant inhibition induced by PEGylated polymer nanoparticles was significantly attenuated. Here, escalations of the PEG coating layer thickness (>3 nm, with a chain-to-chain distance of ≤4 nm) on the colloidal surface were capable of circumventing bioadverse effects. Accordingly, polymer nanoparticles equipped with PEG chains with a molecular weight above 2–5 kDa were compatible with the biophysical function of Alveofact. Overall, PEGylation of polymer nanoparticles presents a promising approach for the development of inhalation nanomedicines revealing negligible effects on the surface activity of the lining layer present in the deep lungs

In Situ Gel Formation in Microporated Skin for Enhanced Topical Delivery of Niacinamide

Although used widely in cosmetic formulations, topical delivery of niacinamide (LogP = −0.35) is unfavorable by conventional means. Poly(lactide-co-glycolide) (PLGA) formulations, can undergo a sol-gel transition triggered by solvent exchange, entrapping molecules and sustaining their release. The current study aims to exploit the ability of PLGA to gel in situ and enhance the topical delivery of niacinamide in microporated skin. In vitro drug permeation studies were performed using vertical Franz diffusion cells. Microporation was performed using Dr. PenTM Ultima A6, where pre-treatment with a 1 mm needle-length for 10 s and a 0.5 mm needle-length for 5 s, both at 13,000 insertions/min were compared. The effect of different grades of PLGA, EXPANSORB® DLG 50-2A (“low” molecular weight), and EXPANSORB® DLG 50-8A (“high” molecular weight) on topical delivery was also determined. Formulations containing PLGA resulted in successful gelation in situ on application over microporated skin. A significantly higher amount of drug was found in the skin with the 0.5 mm treatment for 5 s (892 ± 36 µg/cm2) than with 1 mm for 10 s (167 ± 16 µg/cm2). Hence, the different grades of PLGA were evaluated with 0.5 mm, 5 s treatment, and a significantly larger amount was seen in skin with the higher rather than the lower molecular weight polymer (172 ± 53 µg/cm2)

Evaluating the Controlled Release Properties of Inhaled Nanoparticles Using Isolated, Perfused, and Ventilated Lung Models

Polymeric nanoparticles meet the increasing interest for inhalation therapy and hold great promise to improve controlled drug delivery to the lung. The synthesis of tailored polymeric materials and the improvement of nanoparticle preparation techniques facilitate new perspectives for the treatment of severe pulmonary diseases. The physicochemical properties of such drug delivery systems can be investigated using conventional analytical procedures. However, the assessment of the controlled drug release properties of polymeric nanoparticles in the lung remains a considerable challenge. In this context, the isolated lung technique is a promising tool to evaluate the drug release characteristics of nanoparticles intended for pulmonary application. It allows measurements of lung-specific effects on the drug-release properties of pulmonary delivery systems. Ex vivo models are thought to overcome the common obstacles of in vitro tests and offer more reliable drug release and distribution data that are closer to the in vivo situation

Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying

Hypromellose acetate succinate (HPMCAS) microparticles containing the poorly-water soluble drug celecoxib (CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection. Keywords: Celecoxib, Electrospraying, Hypromellose acetate succinate, Oral drug delivery, Polymeric microparticles, Solvent mixtur