Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

/pdf/principles-of-nanoparticle-design-for-overcoming-biological-4c2c5quqtc.pdf

Principles of nanoparticle design for overcoming biological barriers to drug delivery

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

/pdf/cancer-nanomedicine-progress-challenges-and-opportunities-3dukbks14n.pdf

Cancer nanomedicine: progress, challenges and opportunities.

Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields

In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.

/pdf/poly-lactic-co-glycolic-acid-plga-as-biodegradable-1xyztolf10.pdf

Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

As the human cost of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being witnessed worldwide, the development of broad-spectrum antiviral agents against emerging and re-emerging viruses is seen as a necessity to hamper the spread of infections. Various targets during the viral life-cycle can be considered to inhibit viral infection, from viral attachment to viral fusion or replication. Macromolecules represent a particularly attractive class of therapeutics due to their multivalency and versatility. Although several antiviral macromolecules hold great promise in clinical applications, the emergence of resistance after prolonged exposure urges the need for improved solutions. In the present article, the recent advancement in the discovery of antiviral peptides and polymers with diverse structural features and antiviral mechanisms is reviewed. Future perspectives, such as, the development of virucidal peptides/polymers and their coatings against SARS-CoV-2 infection, standardization of antiviral testing protocols, and use of artificial intelligence or machine learning as a tool to accelerate the discovery of antiviral macromolecules, are discussed.

Broad-Spectrum Antiviral Peptides and Polymers.

Unravelling the anomalous electrical and optical phase-change characteristics in FeTe

Klebsiella pneumoniae (Kp) is one of the most common pathogens in nosocomial infections and is increasingly becoming multiple drug resistant. However, the molecular pathogenesis of Kp in causing tissue injury and dysregulated host defense remains elusive, further dampening the development of novel therapeutic measures. We have previously screened a series of synthetic antimicrobial beta-sheet forming peptides and identified a peptide (IRIKIRIK; ie, IK8L) with a broad range of bactericidal activity and low cytotoxicity in vitro. Here, employing an animal model, we investigated the antibacterial effects of IK8L in acute infection and demonstrated that peritoneal injection of IK8L to mice down-regulated inflammatory cytokines, alleviated lung injury, and importantly, decreased mortality compared to sham-injected controls. In addition, a math model was used to evaluate in vivo imaging data and predict infection progression in infected live animals. Mechanistically, IK8L can kill Kp by inhibiting biofilm formation and modulating production of inflammatory cytokines through the STAT3/JAK signaling both in vitro and in vivo. Collectively, these findings reveal that IK8L may have potential for preventing or treating Kp infection.

/pdf/a-novel-chemosynthetic-peptide-with-b-sheet-motif-43rz7nbqr3.pdf

A novel chemosynthetic peptide with β-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model.

Antimicrobial cationic polycarbonates and polyurethanes have been prepared comprising one or more pendent guanidinium and/or isothiouronium groups. Additionally, antimicrobial particles were prepared having a silica core linked to surface groups comprising a guanidinium and/or isothiouronium group. The cationic polymers and cationic particles can be potent antimicrobial agents against Gram-negative microbes, Gram-positive microbes, and/or fungi.

Antimicrobial guanidinium and thiouronium functionalized polymers

Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2–3 h of alertness coupled with side effects whereas a longer effect of 8–12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

Yi Yan Yang

Papers

Broad-Spectrum Antiviral Peptides and Polymers.

Unravelling the anomalous electrical and optical phase-change characteristics in FeTe

A novel chemosynthetic peptide with β-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model.

Antimicrobial guanidinium and thiouronium functionalized polymers

Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study