Stability For Drug Delivery Research Articles

Rigorous Accounting for Dependent Scattering in Thick and Concentrated Nanoemulsions.

Concentrated and thick oil-in-water nanoemulsions have been observed to become more transparent with increasing oil volume fraction. This study demonstrates rigorously experimentally and numerically that such unusual behavior is due to dependent scattering including not only far-field but also near-field effects. Indeed, when the droplet concentration is sufficiently large, their interparticle distance becomes small compared to the wavelength of light and scattering by a given droplet may be affected by the proximity of others. This situation is referred to as dependent scattering. Light transfer through nanoemulsions and other colloids has previously been modeled by solving the radiative transfer equation accounting for dependent scattering using the static structure factor based on far-field approximations. Here, oil-in-water nanoemulsions were prepared with oil volume fraction ranging between 1 and 20% and a peak droplet radius of 16 nm. The spectral normal-hemispherical transmittance of the different nanoemulsions in 10 mm thick cuvettes was measured experimentally between 400 and 900 nm. Numerical predictions for nonoverlapping randomly distributed nanoscale oil droplets in water and accounting for dependent scattering including near-field effects-using the recently developed radiative transfer with reciprocal transactions (R2T2) method-were in excellent agreement with experimental measurements. Simulations revealed that assuming independent scattering underestimated the normal-hemispherical transmittance even for a relatively small oil volume fraction. Additionally, simulations using the dense medium radiative transfer (DMRT) and static structure factor predicted that dependent scattering prevailed for oil volume fractions slightly greater than those predicted by the R2T2 method. Interestingly, the DMRT method predicted large increases in transmittance when the oil droplet size and volume fraction were larger than 10 nm and 10%, respectively. Finally, simulations also revealed that dependent scattering enables the design of oil-in-water nanoemulsions to backscatter or absorb light by tuning the oil droplet size and volume fraction. The results validate that the R2T2 method could be used to characterize nanoemulsions or to investigate their formation, composition, and stability for drug delivery, food, and cosmetics applications. Future studies could extend the use of the R2T2 method to colloidal suspensions with particles of arbitrary shapes and to radiation transfer of polarized light in turbid media.

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases.

Currently, one of the most significant and rapidly growing unmet medical challenges is the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This challenge encompasses the imperative development of efficacious therapeutic agents and overcoming the intricacies of the blood-brain barrier for successful drug delivery. Here we focus on the delivery aspect with particular emphasis on cell-penetrating peptides (CPPs), widely used in basic and translational research as they enhance drug delivery to challenging targets such as tissue and cellular compartments and thus increase therapeutic efficacy. The combination of CPPs with nanomaterials such as nanoparticles (NPs) improves the performance, accuracy, and stability of drug delivery and enables higher drug loads. Our review presents and discusses research that utilizes CPPs, either alone or in conjugation with NPs, to mitigate the pathogenic effects of neurodegenerative diseases with particular reference to AD and PD.

Quaternary ammonium substituted dextrin‐based biocompatible cationic nanoparticles with ultrahigh pH stability for drug delivery

AbstractCationic nanoparticles (NPs) are preferred for therapeutic applications due to its better uptake by mammalian cells. However, preparing cationic polymeric NPs with stability in wide pH range along with limited toxicity remains a challenge. Dextrin, a carbohydrate‐based natural biological macromolecule holds great potential in biomedical applications. Further, it is an inexpensive and abundant raw material which has high pH stability making it more advantageous over other widely explored macromolecules like chitosan. Herein, we report a simple process for preparing biocompatible cationic dextrin (CD) NPs. A series of CDs were prepared through a single‐step reaction by incorporating quaternary ammonium groups onto the polymeric backbone using varying amount of glycidyltrimethylammonium chloride. Formation of uniform spherical CD NPs having size within 100 nm were achieved by a facile synthesis process of ionic gelation using a biocompatible cross‐linker sodium tripolyphosphate. The prepared CD NPs remained stable across the pH range of 5.5–11 and demonstrated approximately 75% cellular internalization within 6 h. The CD NPs were also found to be both cytocompatible and hemocompatible. Next, the chemotherapeutic drug doxorubicin was encapsulated within CD NPs, which is one of the most common chemotherapeutic agents used for the treatment of various types of cancers including breast, lung, ovarian and bladder. The Dox‐loaded CD NPs showed better drug release at acidic pH conditions and induced more than 80% cell death within 24 h at just 2 μg/ml concentration when tested against HeLa cell lines, thus, proving to be a potential drug delivery vehicle for cancer therapy applications.

Photocrosslinkable Poly(ε-caprolactone)-b -Hyperbranched Polyglycerol (PCL-b -hbPG) with Improved Biocompatibility and Stability for Drug Delivery

The major limitations of nanocarriers for drug delivery are the poor biocompatibility and low stability that may induce the unintended burst release of loaded drugs during blood circulation. To overcome these limitations, a photocrosslinkable amphiphilic block copolymer consisting of hydrophobic poly(ε-caprolactone) (PCL) block and a hydrophilic hyperbranched polyglycerol (hbPG) block with improved biocompatibility and stability for drug delivery is developed. They are readily prepared via UV-triggered chemical crosslinking with 4-hydroxycinnamic acid (CA) modification in the hbPG block. The photocrosslinked hbPG-b-PCL-CA nanoparticles are spherical and the size of nanoparticles is increased to 60 ± 30 nm. Photocrosslinked hbPG-b-PCL-CA nanoparticles exhibit significantly high stability in a physiological buffer and the loaded drug in sustained manner. In addition, photocrosslinked hbPG-b-PCL-CA nanoparticles show good biocompatibility in vitro and in vivo. These data imply the promising potential of photocrosslinked hbPG-b-PCL-CA nanoparticles as nanocarriers for drug delivery.

Microbubble oscillations and stability for drug delivery

Ultrasound contrast agents have been developed from micron size bubbles whose gas core is enclosed by a polymer, lipid or protein shell. Furthermore, specific designs have been developed for drug delivery in which the ultrasound contrast agent acts as drug delivery vehicle. A drug may be suspended in the shell of these agents which is released at a particular site as the microbubble undergoes destruction. Localized delivery depends on the destruction of a sufficient number of bubbles within a confined geometry typically a capillary or small vessel. Experimental evidence suggests the composition and thickness of the shell play important role in the break-up. Break-up scenarios of buckling have been suggested for elastic shell agents and shape stability for fluid shell agents. However, these have not been rigorously examined theoretically. The formulations of contrast agent designed for drug delivery are highlighted including a description of a double polymeric layer design. Shape stability equations for fluid shell agents are derived and analyzed in limiting cases. Furthermore, biological issues related to potential endothelial cell transport and interactions are briefly discussed.