PLGA and PEG based porous microparticles as vehicles for pulmonary somatropin delivery.

Breakthrough advances in protein therapeutics and sustained release systems continue to fuel innovation in novel, non-invasive polymeric platforms for delivery of biologicals. Despite the bench potential and proof-of-concept work, market analysis still shows biologicals to be predominantly injections. Characterized by insufficient secretion of growth hormone by the pituitary gland, growth hormone deficiency (GHD) is a rare disorder. Currently, chronic somatropin (r-hGH) replacement therapy is only available as subcutaneous injections administered several times a week. We aim to prepare large, porous, biodegradable and aerodynamically light microparticles as tunable carriers for pulmonary r-hGH delivery. We developed a range of microparticles using PLGA 5050 1Awith sizes between 5 µm and 13 µm, densities lower than 0.4 g/cc and aerodynamic diameters lower than 6 µm. Polyethylene glycol's multitude of advantages - plasticizing PLGA, improving the biocompatibility of the system and preventing protein burst release - have been extensively studied, making it our excipient (pore-former) of choice. Drug loading was characterized at pH 4.0 (acidic), 5.3 (pI) and pH 7.2 (neutral) and was a result of an interplay of electrostatic and hydrophobic interactions between the polymer and somatropin. Considering the physicochemical interactions, we observed some pH dependent protein unfolding characterized by reduction in intrinsic fluorescence of the Tryptophan 86 residue at 331 nm. The secondary ⍺-helix structure characterized by 2 negative minima at 209 nm and 222 nm in the circular dichroism spectra, was intact at all pH values. R-hGH was released over a period of seven days, and the release profile was a function of the microparticle porosity.

Novel and investigational therapies for wet and dry age-related macular degeneration.

Age-related macular degeneration (AMD) is a macular degenerative eye disease, the major cause of irreversible loss of central vision. In this review, we highlight current progress and future perspectives of novel and investigational therapeutic strategies in the drug pipeline, including anti-vascular endothelial growth factor (VEGF) agents, bispecific antibodies, biosimilars, small molecules, gene therapy, and long-acting drug delivery strategies for both dry and wet AMD. We anticipate that biologics with dual functionalities and combined therapies with long-acting capabilities will lead the wet AMD pipeline. Sustained-release platforms also show potential. However, significant breakthroughs are yet to be made for dry AMD. The personalized approach might be well suited in the scenario of diverse genetic variations in both conditions.

Lipid Nanoparticles Improve the Uptake of α-Asarone Into the Brain Parenchyma: Formulation, Characterization, In Vivo Pharmacokinetics, and Brain Delivery.

Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, α-asarone, for the treatment of brain-related diseases. However, α-asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of α-asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of α-asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free α-asarone, significantly higher levels of α-asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of α-asarone in the plasma, but also transport α-asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound α-asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.

COVID-19 associated complications and potential therapeutic targets.

The global pandemic COVID-19, caused by novel coronavirus SARS-CoV-2, has emerged as severe public health issue crippling world health care systems. Substantial knowledge has been generated about the pathophysiology of the disease and possible treatment modalities in a relatively short span of time. As of August 19, 2020, there is no approved drug for the treatment of COVID-19. More than 600 clinical trials for potential therapeutics are underway and the results are expected soon. Based on early experience, different treatment such as anti-viral drugs (remdesivir, favipiravir, lopinavir/ritonavir), corticosteroids (methylprednisolone, dexamethasone) or convalescent plasma therapy are recommended in addition to supportive care and symptomatic therapy. There are several treatments currently being investigated to address the pathological conditions associated with COVID-19. This review provides currently available information and insight into pathophysiology of the disease, potential targets, and relevant clinical trials for COVID-19.

Pharmaceutical feasibility and flow characteristics of polymeric non-spherical particles.

Last decade has seen emergence of particle shape as a critical design parameter to overcome several long standing problems associated with particulate drug delivery- non-specific drug effects, RES uptake, poor bioavailability, achieving controlled release profiles, predictable degradation profiles, longer circulation time and zero order release kinetics to name a few. Non-spherical particles have been synthesized by techniques ranging from classical solvent evaporation to specialized techniques like film stretching and PRINT®. Non-spherical particles tend to show a difference in macrophage uptake, adhesion to target cells and distribution in vivo. This review also discusses these effects and its implications. Lastly, the impact of particle aspect ratio and other shape-governed parameters on flow properties, dispersion viscosities and other pharmaceutically relevant aspects have been briefly explained. Although there are no thumb rules yet, modern and classical literature on behavior of non-spherical particles has been reviewed and the observations have been trend-lined.