ABSTRACT
Extracellular vesicles (EVs) are small membrane-bound vesicles secreted into the extracellular space by all cell types. EVs transfer their cargo which includes nucleic acids, proteins, and lipids to facilitate cell-to-cell communication. As EVs are released and move from parent to recipient cell, EVs interact with the extracellular matrix (ECM) which acts as a physical scaffold for the organization and function of cells. Recent work has shown that EVs can modulate and act as regulators of the ECM. This review will first discuss EV biogenesis and the mechanism by which EVs are transported through the ECM. Additionally, we discuss how EVs contribute as structural components of the matrix and as components that aid in the degradation of the ECM. Lastly, the role of EVs in influencing recipient cells to remodel the ECM in both pathological and therapeutic contexts is examined.
ABSTRACT
The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions
Subject(s)
Atropine/chemical synthesis , Chitosan/chemical synthesis , Cornea , Drug Delivery Systems/methods , Microspheres , Serum Albumin, Bovine/chemical synthesis , Animals , Atropine/administration & dosage , Atropine/metabolism , Cattle , Cells, Cultured , Chemistry, Pharmaceutical , Chitosan/administration & dosage , Chitosan/metabolism , Cornea/drug effects , Cornea/metabolism , Eye/drug effects , Eye/metabolism , Humans , Mydriasis/drug therapy , Mydriasis/metabolism , Rabbits , Serum Albumin, Bovine/administration & dosage , Serum Albumin, Bovine/metabolismABSTRACT
Antisense molecules that pertain to ribonucleic acid (RNA) and complementary to the messenger RNA (mRNA) are produced by transcription of a given gene. Antisense oligonucleotides have emerged as potential gene-specific therapeutic agents that are currently undergoing evaluation in clinical trials for a variety of diseases. When administered orally, antisense oligionucleotides have poor bioavailability as they are rapidly degraded by the acid in the stomach and by the enzymes in the intestine. Therefore, the enhancement of bioavailability after oral administration is highly desirable. This article shows the enhanced bioavailability of antisense oligonucleotides that targets nuclear factor kappa B (NF-κB) mRNA after encapsulating in an inert, biodegradable albumin polymer matrix that was administered via the oral route into a rat model. The bioavailability of the antisense oligonucleotides to NF-κB in microencapsulated form was compared to the solution form of the drug upon oral administration. The solution form had a low bioavailability of 9%, whereas the bioavailability for the microencapsulated form of the drug increased up to 70%. Moreover, the other pharmacokinetic parameters including half-life (t1/2) and volume of distribution (Vd) increased for the microencapsulated form compared to the solution form of the drug.
Subject(s)
Albumins/chemistry , NF-kappa B/genetics , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/pharmacokinetics , RNA, Messenger/metabolism , Administration, Oral , Animals , Biological Availability , Drug Compounding/methods , Female , Half-Life , Microspheres , NF-kappa B/metabolism , Oligonucleotides, Antisense/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-DawleyABSTRACT
Most ocular surgical procedures take approximately 60 min to complete, the anaesthetic property of the safest drug, tetracaine, is initiated in a few minutes and lasts approximately 10-15 min. The purpose of the present study was to develop an ocular tetracaine formulation which can produce an immediate onset of action and/or longer duration of action during the entire surgical procedure. Tetracaine-loaded microparticle formulation was prepared by the method of spray-drying and characterized in terms of size, zeta potential, morphology, thermal stability and release pattern. The study reports a microparticulate ocular formulation with minimum cytotoxicity and optimum cellular uptake. In addition, microencapsulated tetracaine was found to significantly increase the duration of action of the drug up to 4-fold. Taken together, the results presented in this work described albumin-chitosan microparticles to be an effective delivery platform for ocular anaesthetic agents and a potential treatment of various ocular diseases.
