PLL-g-PEG Polymer Inhibits Antibody-Drug Conjugate Uptake into Human Corneal Epithelial Cells .

Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity.

Early-Stage Formulation Considerations.

When a drug candidate-i.e., a new chemical entity (NCE) or new molecular entity (NME)-is discovered, there is a requirement to identify a vehicle for in vitro and/or in vivo evaluation to assess the activity and/or toxicity of the compound (here we refer to the biologically active compound as the active pharmaceutical ingredient: API).

Novel formulation of glycerin 1% artificial tears extends tear film break-up time compared with Systane lubricant eye drops.

Purpose: To evaluate the effectiveness of glycerin 1% formulated with the novel and proprietary ophthalmic excipient poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) (Eyeon Particle Sciences LLC) in extending tear film break-up time (TFBUT) compared with a market-leading artificial tear formulation of propylene glycol (0.3%) and polyethylene glycol (0.4%) (Systane(®) Lubricant Eye Drops; Alcon, Fort Worth, TX).

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc.

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery.

Ethylene vinyl acetate intravaginal rings for the simultaneous delivery of the antiretroviral UC781 and contraceptive levonorgestrel.

Ethylene vinyl acetate intravaginal rings (IVRs) were prepared by hot-melt compounding and injection moulding. The IVRs contained various levels of the antiretroviral drug UC781 and the contraceptive hormone levonorgestrel. The IVRs were assayed for drug content and related substances, characterized for physical properties, in vitro drug-elution kinetics, photostress stability, and 3-month accelerated storage stability under ICH conditions.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone.

Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

Unlabelled: To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.

Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits.

Identification of xanthurenic acid 8-O-beta-D-glucoside and xanthurenic acid 8-O-sulfate as human natriuretic hormones.

Hormonal regulation of salt excretion and water balance by the kidneys is well documented. Before 1961, it was widely believed that the glomerular filtration rate and the steroid hormone aldosterone controlled sodium balance in the body. In 1961, deWardener et al.

The future of HIV prevention: prospects for an effective anti-HIV microbicide.

Topical microbicides are self-administered products for prevention of HIV transmission, and they present one of the most promising strategies for combating the HIV-AIDS epidemic. The development of microbicides is a long and complicated process, with many hurdles that are unique to this class of product, including challenges in product design, in the conduct and design of clinical trials, and in obtaining licensure of a new class of products intended for use almost exclusively in developing countries. Once they have been registered, there are additional challenges to the marketing and distribution of microbicides.

Microbicides for the prevention of HIV infection in women: an overview of recent trials.

Purpose Of Review: As the HIV/AIDS pandemic continues, the development of new prevention technologies is urgently needed. Microbicides, products applied to genital mucosal surfaces, are being developed to reduce the transmission of HIV during sexual intercourse. Microbicides have been designed to inhibit HIV from the time the virus enters the genital tract to any of the multiple steps in local virus replication.