MRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

Ocular drug delivery has always been a challenge for ophthalmologist and drug delivery scientists due to presence of various anatomical and physiological barriers. Inimitable static and dynamic ocular barriers not only exclude the entry of xenobiotics but also discourage the active absorption of therapeutic agents. An ideal drug delivery system should be designed to enhance drug bioavailability, provide controlled and sustained release of drug at site of action and overcome various ocular barriers. Conventional ophthalmic medications includes the use of topical eye drops and intravitreal injections of anti-VEGF agent for treatment of anterior and posterior segment disorders respectively. Current inventions for the anterior ocular segment disorders like punctum plugs, ocular implants, drug eluting contact lenses, and ocular iontophoresis represent state of the art inventions for sustained and controlled drug release. Parallel efforts for ocular drug delivery technologies for back of the eye disorders have resulted in the approval of various intravitreal implants. Novel drug delivery technologies including nanoparticles, nanomicelles, dendrimers, microneedles, liposomes and nanowafers are increasingly studied for anterior and posterior disorders. To achieve patient compliance for back of the eye disorders, novel approaches for noninvasive delivery of potent therapeutic agents are on a rise. In this review article we discuss the past successes, present inventions and future challenges in ocular drug delivery technologies. This expert opinion also discusses the future challenges for ocular drug delivery systems and the clinical translatable potential of nanotechnology from benchtop to the bedside. SIGNIFICANCE STATEMENT N/A

Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or “smart” NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.

Ocular barriers hinder drug delivery and reduce drug bioavailability. This article focuses on enhancing drug absorption across the corneal and conjunctival epithelium. Both, transporter targeted pr...

Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.

Active targeting and overcoming multi-drug resistance (MDR) can be some of the important attributes of targeted therapy for metastatic breast cancer (MBC) and triple-negative breast cancer (TNBC) treatment. In this study, we constructed a hyaluronic acid (HA)-decorated mixed nanomicelles-encapsulating chemotherapeutic agent paclitaxel (PTX) and P-glycoprotein inhibitor ritonavir (RTV). HA was conjugated to poly (lactide) co-(glycolide) (PLGA) polymer by disulfide bonds (HA-ss-PLGA). HA is a natural ligand for CD44 receptors overexpressed in breast cancer cells. Disulfide bonds undergo rapid reduction in the presence of glutathione, present in breast cancer cells. The addition of RTV can inhibit the P-gp and CYP3A4-mediated metabolism of PTX, thus aiding in reversing MDR and sensitizing the cells toward PTX. An in vitro uptake and cytotoxicity study in MBC MCF-7 and TNBC MDA-MB-231 cell lines demonstrated the effective uptake of the nanomicelles and drug PTX compared to non-neoplastic breast epithelium MCF-12A cells. Interestingly, in vitro potency determination showed a reduction in mitochondrial membrane potential and reactive oxygen species in breast cancer cell lines, indicating effective apoptosis of cancer cells. Thus, stimuli-sensitive nanomicelles along with HA targeting and RTV addition can effectively serve as a chemotherapeutic drug delivery agent for MBC and TNBC.