A comprehensive review of challenges and advances in exosome-based drug delivery systems.

Exosomes or so-called natural nanoparticles have recently shown enormous potential for targeted drug delivery systems. Several studies have reported that exosomes as advanced drug delivery platforms offer efficient targeting of chemotherapeutics compared to individual polymeric nanoparticles or liposomes. Taking structural constituents of exosomes, , proteins, nucleic acids, and lipids, into consideration, exosomes are the most promising carriers as genetic messengers and for treating genetic deficiencies or tumor progression.

Targeting Allosteric Site of PCSK9 Enzyme for the Identification of Small Molecule Inhibitors: An In Silico Drug Repurposing Study.

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels.

Rapidly Dissolving Trans-scleral Microneedles for Intraocular Delivery of Cyclosporine A.

Cyclosporine A (CsA) is a cyclic peptide immunosuppressant drug that is beneficial in the treatment of various ocular diseases. However, its ocular bioavailability in the posterior eye is limited due to its poor aqueous solubility. Conventional CsA formulations such as a solution or emulsion permeate poorly across the eye due to various static and dynamic barriers of the eye.

Pharmacological inhibition of KDM1A/LSD1 enhances estrogen receptor beta-mediated tumor suppression in ovarian cancer.

Ovarian cancer (OCa) is the most lethal gynecologic cancer. Emerging data indicates that estrogen receptor beta (ERβ) functions as a tumor suppressor in OCa. Lysine-specific histone demethylase 1A (KDM1A) is an epigenetic modifier that acts as a coregulator for steroid hormone receptors.

Development of optimal in vitro release and permeation testing method for rectal suppositories.

Currently there are no compendial assays for testing drug release from rectal suppositories. It is therefore essential to study different in vitro release testing (IVRT) and in vitro permeation testing (IVPT) methods for identifying a suitable technique to compare in vitro drug release and to predict in vivo performance of rectal suppositories. In the present study, three different rectal suppository formulations of mesalamine (CANASA, Generic, and In-house) were studied for in vitro bioequivalence.

Biomedical applications of three-dimensional bioprinted craniofacial tissue engineering.

Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures.

Advances in in-vitro bioequivalence testing methods for complex ophthalmic generic products.

The United States Food and Drug Administration (USFDA) demands that the generic industry prove topical ocular products' pharmaceutical and bioequivalence (BE). In contrast to generic oral drugs, topical ocular product BE testing has proved difficult. New generic versions are compared to an authorized drug product known as a Reference Listed Drug (RLD) to demonstrate their bioequivalence.

Natural proteins and polysaccharides in the development of micro/nano delivery systems for the treatment of inflammatory bowel disease.

Treatments for inflammatory bowel disease (IBD) are typically immunosuppressive. Despite a range of treatment options, limited efficacy, systemic toxicities like bone marrow suppression, infections and malignancy are their serious setbacks. There exists an unmet medical need for novel therapeutic agents without safety concerns resulting from chronic, systemic immunosuppression.

Natural Product-Based Nanomedicine in Treatment of Inflammatory Bowel Disease.

Many synthetic drugs and monoclonal antibodies are currently in use to treat Inflammatory Bowel Disease (IBD). However, they all are implicated in causing severe side effects and long-term use results in many complications. Numerous in vitro and in vivo experiments demonstrate that phytochemicals and natural macromolecules from plants and animals reduce IBD-related complications with encouraging results.

Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability.

Cyclodextrin complex of nintedanib was prepared aiming for increased bio-activity and improved transport across intestinal membrane with reduced p-glycoprotein (p-gp) efflux. Based on preliminary phase solubility studies and molecular modeling, sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD, Captisol) was selected to prepare inclusion complex. Complexation was confirmed using FTIR, 1H NMR, DSC, and XRD.

Development and Evaluation of Talazoparib Nanoemulsion for Systemic Therapy of -mutant Cancer.

Aim: This is a debut study report on talazoparib (BMN-673)-loaded nanoemulsion (TZNE) for parenteral administration.

Materials And Methods: TZNE (0.05% drug, 151.

Development and validation of a high-performance liquid chromatography method for the quantification of talazoparib in rat plasma: Application to plasma protein binding studies.

A sensitive and selective RP-HPLC method has been developed and validated for the quantification of a highly potent poly ADP ribose polymerase inhibitor talazoparib (TZP) in rat plasma. Chromatographic separation was performed with isocratic elution method. Absorbance for TZP was measured with a UV detector (SPD-20A UV-vis) at a λ of 227 nm.

Safety and toxicity of nanomaterials for ocular drug delivery applications.

Multifunctional nanomaterials are rapidly emerging for ophthalmic delivery of therapeutics to facilitate safe and effective targeting with improved patient compliance. Because of their extremely high area to volume ratio, nanomaterials often have physicochemical properties that are different from those of their larger counterparts. There exists a complex relationship between the physicochemical properties (composition, size, shape, charge, roughness, and porosity) of the nanomaterials and their interaction with the biological system.

Recent Advances in Topical Ocular Drug Delivery.

Topical ocular drug delivery has been considered to be an ideal route of administration for treatment of ocular diseases related to the anterior segment of the eye. However, topical ocular delivery is a challenging task because of barriers such as nasolacrimal drainage, corneal epithelium, blood-ocular barriers, and metabolism in the eye. Approaches to improve ocular bioavailability include physical approaches such as formulations of drugs as solutions (Zymaxid(™)), suspensions (Zigran(®)), gels (Akten(®)) and chemical approaches such as prodrugs (Xalatan(™)), chemical delivery systems, and soft drugs.

Interactions between carbon nanotubes and bioactives: a drug delivery perspective.

Applications of carbon nanotubes (CNTs) in the biomedical arena have gained increased attention over the past decade. Surface engineering of CNTs by covalent and noncovalent modifications enables site-specific drug delivery and targeting. CNTs are available as single-, double-, triple-, and multiwalled carbon nanotubes (SWCNTs, DWCNTs, TWCNTs, and MWCNTs, respectively) and have unique physicochemical properties, including a high surface area, high loading efficiency, good biocompatibility, low toxicity, ultra lightweight, rich surface chemistry, non-immunogenicity, and photoluminescence.

Challenges in SN38 drug delivery: current success and future directions.

Introduction: Clinical use of SN38 is limited by its poor aqueous solubility and hydrolysis of the lactone ring at pH > 6 to inactive carboxylate form. A variety of drug delivery systems have been developed to improve the solubility and stability of SN38, and reduce its toxicity. A few noteworthy formulations with some success in initial phases of clinical trials are reported.

Transcriptional targeting of human liver carboxylesterase (hCE1m6) and simultaneous expression of anti-BCRP shRNA enhances sensitivity of breast cancer cells to CPT-11.

Background: The major factor limiting the efficacy of breast cancer chemotherapy is multidrug resistance due to overexpression of the breast cancer resistance protein ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2). We hypothesized that conversion of camptothecin-11 (CPT-11) to its highly cytotoxic metabolite SN-38 by a mutant human carboxyl esterase (hCE1m6) specifically in cancer cells and inhibition of ABCG2 by anti-ABCG2 short hairpin RNA, leads to accumulation of a higher concentration of SN-38, resulting in higher therapeutic efficacy and less toxicity to normal cells.

Materials And Methods: A mutant human carboxyl esterase hCE1m6 with human telomerase reverse transcriptase promoter was integrated into the VISA (VP16-Gal4-WPRE) amplification system.

Nanomedicine scale-up technologies: feasibilities and challenges.

Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage.

Zein in controlled drug delivery and tissue engineering.

Controlled delivery of a bioactive to specific organ, cellular and sub-cellular level is a desired feature of a drug carrier system. In order to achieve this goal, formulation scientists search for better alternatives of biomaterials to deliver the therapeutics in more precise and controlled manner in vivo. Zein, a plant protein obtained from corn, is a useful biomaterial for several industrial applications including agriculture, cosmetics, packaging and pharmaceuticals.

SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer.

SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether β-cyclodextrin (SBEβCD), hydroxypropyl β-cyclodextrin, randomly methylated β-cyclodextrin, and methyl β-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008).

Hyaluronic acid-decorated PLGA-PEG nanoparticles for targeted delivery of SN-38 to ovarian cancer.

Background: Extreme hydrophobicity and poor stability of SN-38, a highly potent topoisomerase I inhibitor, has prevented its clinical use. Its encapsulation into nanoparticles may be a way to overcome these problems. Here we report the use of SN-38-loaded hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) for targeted ovarian cancer therapy.

Comparative evaluation of small-molecule chemosensitizers in reversal of cisplatin resistance in ovarian cancer cells.

Cisplatin-resistance is one of the major challenges in the treatment of epithelial ovarian cancer. Small-molecule chemosensitizers provide a therapeutically feasible approach to overcome cisplatin resistance in ovarian cancer. However, proper selection of chemosensitizer is of prime importance owing to phenotypic differences in cisplatin-resistant ovarian cancers.

Differential expression of caveolin-1 and caveolin-3: potential marker for cardiac toxicity subsequent to chronic ozone inhalation.

Earlier studies from our laboratory have shown myocardial dysfunction subsequent to chronic O(3) exposure in rats may be associated with a decrease in antioxidant reserve and increased activity of inflammatory mediators. The present study tested the hypothesis that O(3)-induced cardiac dysfunction in healthy adult rats may be due to changes in caveolin-1 and caveolin-3 levels. Sprague-Dawley rats were exposed 8 h/day for 28 and 56 days to filtered air or 0.

Recent trends in cancer drug resistance reversal strategies using nanoparticles.

Introduction: Resistance to chemotherapy is a major obstacle in the successful amelioration of tumors in many cancer patients. Resistance is either intrinsic or acquired, involving mechanisms such as genetic aberrations, decreased influx and increased efflux of drugs. Strategies for the reversal of resistance involve the alteration of enzymes responsible for drug resistance, the modulation of proteins regulating apoptosis mechanisms and improving the uptake of drugs using nanotechnology.