Reservoir For Sustained Release Research Articles

Bone-Targeted Delivery of Novokinin as an Alternative Treatment Option for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory bone destructive disorder that is orchestrated by multiple systems in the body, including Renin-Angiotensin System (RAS) and arachidonic acid (ArA) pathway. Current therapeutic options are not highly effective and are associated with severe side effects, including cardiovascular complications. Therefore, new safe and effective disease modulators are seriously needed. In this study, we investigate the anti-inflammatory effects of a synthetic peptide, novokinin, through Angiotensin Type (II) receptor (AT2R). Peptide drugs like novokinin suffer from plasma instability and short half-life. Thus, we developed a novel bone targeting novokinin conjugate (Novo Conj). It uses the bone as a reservoir for sustained release and protection from systemic degradation, improving stability and enhancing pharmacological efficacy. We tested Novo Conj’s anti-inflammatory effects in adjuvant-induced arthritis (AIA) rat model to prove our hypothesis by measuring various RAS and ArA pathway components. We observed that inflammation causes a significant imbalance in cardioprotective RAS components like ACE2, AT2R, and Ang 1-7 and increases the ArA inflammatory metabolites like hydroxyeicosatetraenoic acids (HETEs). Treatment with novokinin or Novo Conj restores balance in the RAS and favors the production of different epoxyeicosatrienoic acids (EETs), which are anti-inflammatory mediators. This study demonstrated that the bone-targeted delivery improved the stability and enhanced the anti-inflammatory effects of the parent peptide novokinin in AIA. These observations offer an efficacious alternative therapy for managing RA.

Biphasic Drug Release from Rolled-Up Gelatin Capsules with a Cylindrical Cavity.

Biphasic drug delivery systems are used for quick release of a specific amount of drug for immediate amelioration of a patient’s state, followed by sustained release, to avoid repeated administration. This type of delivery is often necessary for pain management and the treatment of many pathologies, such as migraines, hypertension, and insomnia. In this work, we propose a novel architecture of a biphasic release media that does not need the rapidly disintegrating layer and that allows for easily setting the sustained release rate. A drug-containing capsule is made by rolling up a thermally crosslinked gelatin strip on which drug reservoirs are formed by casting. The quick-release reservoir (QRR) is placed at the strip’s extremity, from which the rolling starts, while the sustained-release reservoir (SRR) is formed in the middle part of the strip. The strip is rolled around a cylinder that is a few millimeters wide, which is removed after rolling. The roll is stabilized by transglutaminase-catalyzed crosslinking of the consecutive shells. A biphasic release is successfully demonstrated with the use of model fluorescent drugs for single-dye and double-dye systems in phosphate-buffered saline (PBS) solution with pH = 7.4. In vitro, the drug from the QRR, placed at the walls of the cavity of the roll, is released immediately upon the capsule’s contact with the PBS solution. The drug from the SRR, embedded between the roll’s layers, diffuses steadily, with the lag time defined by the radial position of the reservoir.

Ultrasmall AgNP-Impregnated Biocompatible Hydrogel with Highly Effective Biofilm Elimination Properties.

Ultrasmall silver nanoparticles (AgNPs; size < 3 nm) have attracted a great deal of interest as an alternative to commercially available antibiotics due to their ability to eliminate a wide range of microbial pathogens. However, most of these ultrasmall AgNPs are highly reactive and unstable, as well as susceptible to fast oxidation. Therefore, both the stability and toxicity remain major shortcomings for their clinical application and uptake. To circumvent these problems, we present a novel strategy to impregnate ultrasmall AgNPs into a biocompatible thermosensitive hydrogel that enables controlled release of silver alongside long-term storage stability and highly potent antibacterial activity. The advantage of this strategy lies in the combination of a homogenous dispersion of AgNPs in a hydrogel network, which serves as a sustained-release reservoir, and the unique feature of ultrasmall AgNP size, which provides an improved biofilm eradication capacity. The superior biofilm dispersion properties of the AgNP hydrogel is demonstrated in both single-species and multispecies biofilms, eradicating ∼80% of established biofilms compared to untreated controls. Notably, the effective antibacterial concentration of the formulation shows minimal toxicity to human fibroblasts and keratinocytes. These findings present a promising novel strategy for the development of AgNP hydrogels as an efficient antibacterial platform to combat resistant bacterial biofilms associated with wound infections.

Synthesis and Characterization of Peptidomimetic Self-Assembled Biodegradable Nanoparticles

AbstractNanoparticles (NPs) are being used extensively for tumor drug delivery. These devices offer the advantage of their size, protection of the encapsulated species, and biodegradability to prevent accumulation in the interstitium. Our laboratory has synthesized polylactide fumarate (PLAF, PLGF) macromers capable of self-assembling into biodegradable and biocompatible NPs with average particle size of 280 nm. To assess the possibility of further decreasing the particle size and distribution of PLGF NPs, the polymers were conjugated with the peptide sequence Cys-Val-Val-Val-Val-Val-Val-Lys-Lys (CV6K2), which is known to self-assemble in aqueous solution into vesicles of about 50-60 nm in size. The results indicate that the PLGF-CV6K2 conjugates are capable of self-assembling into NPs of 100 nm in diameter. The NPs are proposed as having a bilayer structure, with peptide chains facing the aqueous environment and the polymer chains compacted in an internal hydrophobic layer. Degradation kinetics and release profiles show that the NPs could effectively retain and release Paclitaxel up to 30 days until completely degraded. The NPs act as reservoirs for sustained release of the active agent by diffusion and degradation of the matrix when taken up by tumor cells.

Anticonvulsant Effect of Systemically Administered γ-Aminobutyric Acid (GABA)-Containing Liposomes in Rats Induced to Seizure by Amygdaloid Electrical Stimulation

AbstractThe effects of γ-aminobutyric acid (GABA)-containing liposomes were examined in amygdaloid kindled rats. One hr after intraperitoneal administration of GABA, liposomes (LIPO), or GABA-containing LIPO (GABA-L), the animals were stimulated at the generalized seizure triggering threshold. GABA-L had a dose-dependent anticonvulsant effect, whereas no effect was seen with either GABA or LIPO alone. The effect of GABA-L may be due to the ability of LIPO to act as a sustained release reservoir.