Stability of ranibizumab during continuous delivery from the Port Delivery Platform.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system that has the potential to reduce treatment burden in patients with retinovascular diseases. The Port Delivery Platform (PD-P) implant is a permanent, indwelling device that can be refilled in situ through a self-sealing septum and is designed to continuously deliver ranibizumab by passive diffusion through a porous titanium release control element. We present results for the studies carried out to characterize the stability of ranibizumab for use with the PD-P.

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility.

In-vitro characterization of ranibizumab release from the Port Delivery System.

The Port Delivery System with ranibizumab (PDS) consists of an implant that is a permanent, indwelling drug delivery device that can be refilled through a self-sealing septum and is designed to continuously release a customized formulation of ranibizumab into the vitreous by passive diffusion through a porous titanium release control element. Target release rates of ranibizumab via the implant used in studies of the PDS in patients with neovascular age-related macular degeneration were selected based on clinical and pharmacokinetic (PK) data from previously conducted intravitreal ranibizumab injection studies. In-vitro testing was performed to verify release rates with a range of ranibizumab concentrations before the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) trials of the PDS.

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD).

Design: Phase 3, open-label, randomized, visual acuity assessor-masked noninferiority and equivalence trial.

Participants: Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy.

A custom virtual reality training solution for ophthalmologic surgical clinical trials.

We present a summary of the development and clinical use of two custom designed high-fidelity virtual-reality simulator training platforms. This simulator development program began in 2016 to support the phase III clinical trial Archway (ClinicalTrials.gov identifier, NCT03677934) intended to evaluate the Port Delivery System (PDS) developed by Genentech Inc.

Nonclinical Toxicology and Biocompatibility Program Supporting Clinical Development and Registration of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration.

The Port Delivery System with ranibizumab (PDS) is an investigational drug delivery system designed to provide continuous intravitreal release of ranibizumab for extended durations. The PDS consists of a permanent, surgically placed, refillable intraocular implant; a customized formulation of ranibizumab; and ancillary devices to support surgery and refill procedures. A toxicology program was conducted to evaluate the ocular toxicology and biocompatibility of the PDS to support its clinical development program and product registrational activities.

Virtual Reality Becomes a Reality for Ophthalmologic Surgical Clinical Trials.

The Port Delivery System with ranibizumab (PDS) is an innovative, investigational drug delivery system designed for continuous delivery of ranibizumab into the vitreous to maintain therapeutic drug concentrations for extended durations. The phase 2 Ladder trial (NCT02510794) tested the efficacy of three customized formulations of ranibizumab in patients with neovascular age-related macular degeneration, and the phase 3 Archway trial (NCT03677934) will further assess the safety and efficacy of PDS 100 mg/mL with fixed 24-week refills. The insertion of the PDS implant into the vitreous cavity and subsequent refill-exchange of the drug require procedural skills that are not directly transferable from everyday experience for most eye surgeons today.

Suture fixation of migrated septal occluder device to prevent further migration: a simple surgical technique.

As the use of percutaneous intervention is increasing for the closure of the atrial septal defect, the procedure related complications are also on rise, migration of the device being most common. The migrated devices with failed percutaneous retrieval must be removed surgically under cardiopulmonary bypass. During establishment of cardiopulmonary bypass, the handling of heart may cause further migration of the device into other chambers of heart which leads to difficulty in finding and retrieval of the device.

Styrenic block copolymers for biomaterial and drug delivery applications.

The use of styrenic block copolymers has undergone a renaissance as a biomaterial and drug delivery matrix. The early promise posed by the physical and biological properties of these block copolymers for implantable medical devices was not met. However, there has been an increased understanding of the role of microphase separation on the mediation of the biological response.

Evaluation of acrylate-based block copolymers prepared by atom transfer radical polymerization as matrices for paclitaxel delivery from coronary stents.

Acrylate-based block copolymers, synthesized by atom transfer radical polymerization (ATRP) processes, were evaluated as drug delivery matrices for the controlled release of paclitaxel from coronary stents. The polymers were multiblock copolymers consisting of poly(butyl acrylate) or poly(lauryl acrylate) soft blocks and hard blocks composed of poly(methyl methacrylate), poly(isobornyl acrylate), or poly(styrene) homo- or copolymers. Depending on the ratio of hard to soft blocks in the copolymers, coating formulations were produced that possessed variable elastomeric properties, resulting in stent coatings that maintained their integrity when assessed by scanning electron microscopy (SEM) imaging of overexpanded stents.

NMR characterization of paclitaxel/poly (styrene-isobutylene-styrene) formulations.

TAXUStrade mark is a coronary drug-eluting stent system utilizing a formulation consisting of cellular-target drug paclitaxel and poly (styrene-isobutylene-styrene) (SIBS). The present study investigates the interaction and interfacial dynamics of paclitaxel incorporated in a nano-polymeric matrix system. Solution and solid-state CP/MAS NMR experiments were designed to characterize the microstructure of heterogeneous drug-polymer mixtures in terms of its composition, molecular mobility, molecular order, paclitaxel-SIBS molecular interactions, and molecular mobility of the drug in the polymer matrix.

Controlled delivery of paclitaxel from stent coatings using poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and its acetylated derivative.

A poly(styrene-b-isobutylene-b-styrene) (SIBS) triblock polymer is employed as the polymer drug carrier for the TAXUS Express2 Paclitaxel-Eluting Coronary Stent system (Boston Scientific Corp.). It has been shown that the release of paclitaxel (PTx) from SIBS can be modulated by modification of either drug-loading ratio or altering the triblock morphology by blending.

Physical characterization of controlled release of paclitaxel from the TAXUS Express2 drug-eluting stent.

The polymer carrier technology in the TAXUS drug-eluting stent consists of a thermoplastic elastomer poly(styrene-b-isobutylene-b-styrene) (SIBS) with microphase-separated morphology resulting in optimal properties for a drug-delivery stent coating. Comprehensive physical characterization of the stent coatings and cast film formulations showed that paclitaxel (PTx) exists primarily as discrete nanoparticles embedded in the SIBS matrix. Thermal and chemical analysis did not show any evidence of solubility of PTx in SIBS or of any molecular miscibility between PTx and SIBS.