Sai Priyanka Kodam

Bio: Sai Priyanka Kodam is an academic researcher from Stanford University. The author has contributed to research in topics: Medicine & Rejuvenation. The author has an hindex of 1, co-authored 2 publications receiving 11 citations.

Microbubbles versus Extracellular Vesicles as Therapeutic Cargo for Targeting Drug Delivery.

Abstract: Extracellular vesicles (EVs) and microbubbles are nanoparticles in drug-delivery systems that are both considered important for clinical translation. Current research has found that both microbubbles and EVs have the potential to be utilized as drug-delivery agents for therapeutic targets in various diseases. In combination with EVs, microbubbles are capable of delivering chemotherapeutic drugs to tumor sites and neighboring sites of damaged tissues. However, there are no standards to evaluate or to compare the benefits of EVs (natural carrier) versus microbubbles (synthetic carrier) as drug carriers. Both drug carriers are being investigated for release patterns and for pharmacokinetics; however, few researchers have focused on their targeted delivery or efficacy. In this Perspective, we compare EVs and microbubbles for a better understanding of their utility in terms of delivering drugs to their site of action and future clinical translation.

Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications

Abstract: The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.

Diagnostic and Therapeutic Potential of Extracellular Vesicles.

Abstract: Extracellular vesicles (EVs) are naturally phospholipid enclosed nanovesicles released by many cells in the body. They are stable in circulation, have low immunogenicity, and act as carriers for functionally active biological molecules. They interact with target organs and bind to the receptors. Their target specificity is important to use EVs as noninvasive diagnostic and prognostic tools. EVs play a vital role in normal physiology and cellular communication. They are known to protect their cargo from degradation, which makes them important drug carriers for targeted drug delivery. Using EVs with markers and tracking their path in systemic circulation can be revolutionary in using them as diagnostic tools. We will discuss the scope of this in this paper. Although there are limitations in EVs isolation and storage, their high biocompatibility will fuel more innovations to overcome these challenges.

Exosome engineering for efficient and targeted drug delivery: current status and future perspective.

Abstract: Exosomes are membrane-bound vesicles that are released by most cells. They carry nucleic acids, cytokines, growth factors, proteins, lipids, and metabolites. They are responsible for inter- and intra-cellular communications and their role in drug delivery is well defined. Exosomes have great potential for therapeutic applications, but the clinical use is restricted due to limitations in standardized procedures for isolation, purification, and drug delivery. Bioengineering of exosomes could be one approach to achieve standardization and reproducible isolation for clinical use. Exosomes are important transporters for targeted drug delivery because of their small size, stable structure, non-immunogenic, non-toxic nature, and the ability to carry a wide variety of compounds. These features of exosomes can be enhanced further by bioengineering. In this review, possible exosome bioengineering approaches, their biomedical applications, and targeted drug delivery are being discussed. Abstract figure legend Exosomes Bioengineering for efficient and targeted drug delivery. Reprogrammed exosomes release the cargo of growth and regenerative factors more effectively than naïve exosomes for tissue engineering and can be used as a drug delivery platform. This article is protected by copyright. All rights reserved.

Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis

Abstract: Abstract The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities.

Abstract: Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields' utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

Engineering stem cells to produce exosomes with enhanced bone regeneration effects: an alternative strategy for gene therapy

Abstract: Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as "cell-free" therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency.In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells.In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy.

Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications

Abstract: The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.