Ocular Drug Delivery: Present Innovations and Future Challenges.

Ocular drug delivery has always been a challenge for ophthalmologists and drug-delivery scientists due to the presence of various anatomic and physiologic barriers. Inimitable static and dynamic ocular barriers not only exclude the entry of xenobiotics but also discourage the active absorption of therapeutic agents. Designing an ideal delivery scheme should include enhanced drug bioavailability and controlled release of drug at the site of action, which can overcome various ocular barriers. Conventional ophthalmic medications include the use of topical eye drops and intravitreal injections of anti-vascular endothelial growth factor agent for treatment of anterior and posterior segment disorders, respectively. Current inventions for anterior ocular segment disorders such as 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 the rise. In this review article, we discuss 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 bedside.

Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues.

The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD. The bioavailability of curcumin is negligible due to its poor aqueous solubility. The purpose of this work is to develop an aqueous nanomicellar drop formulation of curcumin (CUR-NMF) for back of the eye delivery utilizing hydrogenated castor oil (HCO-40) and octoxynol-40 (OC-40) to treat AMD. A full factorial design was performed with JMP software analysis to optimize the formulation size, polydispersity index (PDI), entrapment efficiency, loading, and precipitation. MTT and LDH assays on human retinal pigmented epithelial (D407) cells revealed that 5-10 µM CUR-NMF dose is safe for ophthalmic use. Furthermore, CUR-NMF exhibited significant protection of retinal (D407) cells against H2O2-induced oxidative stress. In vitro drug release kinetics suggested a sustained drug release profile indicating a long-term protection ability of CUR-NMF against oxidative stress to retinal cells. In addition, an ELISA suggested that CUR-NMF significantly reduces vascular endothelial growth factor (VEGF) release in D407 cell line, hence diminishes the risk of angiogenesis. Collectively, these results suggest that the proposed CUR-NMF can be tremendously effective in treating both types of AMD.

A comprehensive review on the fate and impact of antibiotic residues in the environment and public health: A special focus on the developing countries.

The widespread application of antibiotics in human and veterinary medicine has led to the pervasive presence of antibiotic residues in the environment, posing a potential hazard to public health. This comprehensive review aims to scrutinize the fate and impact of antibiotic residues, with a particular focus on the context of developing nations. The investigation delves into the diverse pathways facilitating the entry of antibiotics into the environment and meticulously examines their effects on human health. The review delineates the current state of antibiotic residues, evaluates their exposure in developing nations, and elucidates existing removal methodologies. Additionally, it probes into the factors contributing to the endurance and ecotoxicity of antibiotic residues, correlating these aspects with usage rates and associated mortalities in these nations. The study also investigates removal techniques for antibiotic residues, assessing their efficiency in environmental compartments. The concurrent emergence of antibiotic-resistant bacteria, engendered by antibiotic residues, and their adverse ecological threats underscore the necessity for enhanced regulations, vigilant surveillance programs, and the adoption of sustainable alternatives. The review underlines the pivotal role of public education and awareness campaigns in promoting responsible antibiotic use. The synthesis concludes with strategic recommendations, strengthening the imperative for further research encompassing comprehensive monitoring, ecotoxicological effects, alternative strategies, socio-economic considerations, and international collaborations, all aimed at mitigating the detrimental effects of antibiotic residues on human health and the environment. PRACTITIONER POINTS: Antibiotic residues are widely distributed in different environmental compartments. Developing countries use more antibiotics than developed countries. Human and veterinary wastes are one of the most responsible sources of antibiotic pollution. Antibiotics interact with biological systems and trigger pharmacological reactions at low doses. Antibiotics can be removed using modern biological, chemical, and physical-chemical techniques.

Self-Assembled Nanomicelles to Enhance Solubility and Anticancer Activity of Etoposide.

It is hypothesized that etoposide/VP-16 nanomicellar formulation (VP-16 NMF) utilizing D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) can improve etoposide solubility and anticancer activity. The following four different concentrations of TPGS: 3, 6, 8, and 10 wt% were used to solubilize the drug. Among these four formulations, 10 wt% of TPGS loaded with VP-16 NMF dramatically enhanced etoposide apparent solubility by 26-folds compared with the native drug. The physicochemical properties of the optimized formulation were further analyzed by dynamic light scattering, X-ray powder diffraction, scanning electron microscopy, proton nuclear magnetic resonance (1HNMR) and Fourier transform infrared spectroscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) was used to assess solubility and intracellular uptake of the drug from the NMF. Cell viability assay ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium solution [MTS]) was performed on MCF-7 and MCF-10A cell lines to assess intracellular uptake and anticancer activity of etoposide. The MTS assay results showed that the VP-16 NMF platform provides a higher anticancer activity than the native VP-16 on the MCF-7 cells line as it integrates a dual anticancer activity of VP-16 and TPGS. LC-MS/MS data showed a threefold increase in cellular uptake of VP-16 NMF in MCF-7 cell line compared with the native etoposide. These data suggest that an optimal TPGS concentration can improve VP-16 bioavailability and efficacy with potential benefits for chemotherapy.

Long-term delivery of protein and peptide therapeutics for cancer therapies.

Introduction: Proteins and peptides are prominent therapeutic agents, which are effective in number of ailments. Long-term delivery of protein and peptide therapeutics requires polymeric encapsulation to protect from degradation and for its sustained release. However, results from encapsulation of protein macromolecules in dynamic delivery systems report unreliable clinical outcome, indicating ease of degradation, low permeability, and serious immune responses. A specifically targeted delivery system as tumor or cancer theranostics may surpass these limitations. Areas covered: This review covers recent advancements in approaches involving conjugated protein nano-formulations as targeting delivery technology for various ailments encompassing mostly cancer treatment options. Progressions in targeted chemotherapeutics, protein nanoparticles, peptide nanoparticles, lipidation, and antibody drug-conjugates are discussed. Expert opinion: Significant expansions have been made in forming new generation of antitumor-recombinant proteins, which proves a milestone of advancements for more potent and explicit cancer therapies. However, transformation of biologics from laboratory to clinical trials is an immense challenge, because of drop in efficiency of drug-loading, poor reproducibility of nanoparticles, inadequate information regarding long-term toxicity and insufficient pharmacokinetics data. Hence, early stage tumor diagnosis with précised drug delivery to tumor site is crucial for protein- and peptide- based therapeutics for cancer.