Expert Opinion on Drug Delivery最新文献

Introduction: The substantial acceleration in healthcare spending together with the expenditures to manage the COVID19 pandemic demand drug delivery solutions that enable a flexible care setting for high-dose monoclonal antibodies (mAbs) in oncology.

Areas covered: This expert opinion introduces an analogue-based framework applied to guide decision-making for associated product improvements for mAb medications that are either already authorized or in late-stage clinical development. The four pillars of this framework comprise (1) the drug delivery profile of current and emerging treatments in the market, (2) the needs and preferences of people treated with mAbs, (3) existing healthcare infrastructures, and (4) country-dependent reimbursement and procurement models. The following product optimization examples for mAb-based treatments are evaluated based on original research and review articles in the field: subcutaneous formulations, an established drug delivery modality to reduce parenteral dosing complexity, fixed-dose combinations, an emerging concept to complement combination therapy, and (connected) on-body delivery systems, an identified future opportunity to support dosing outside of a controlled healthcare institutional environment.

Expert opinion: Leveraging existing synergies and learnings from other disease areas is a measure to reduce associated development and commercialization costs and thus to provide sustainable product offerings already at the initial launch of a medication.

Introduction: Glioblastoma (GB) is one of the most challenging central nervous system (CNS) tumors in treatment options and response, urging the development of novel management strategies. The anti-alcoholism drug, disulfiram (DS), has a potential anticancer activity, and its complex mechanism of action is assumed to be well exploited against the heterogeneous GB.

Area covered: Through a systematic literature review about repositioning DS to GB treatment, an evaluation of the clinical, pharmacological, and formulation strategies is provided to specify the challenges of drug delivery and thus to advance its clinical translation. From six databases, 35 articles were selected, including case report (1); clinical trials (3); original articles mainly representing in vitro and preclinical pharmacological data, and 10 dealing with technological approaches.

Expert opinion: The repositioning of DS in GB treatment is facing drug and tumor-associated limitations due to the oral drug's low bioavailability, unwanted metabolism, and inefficient delivery to brain-tumor tissue. Development strategies using molecular encapsulation of DS and the parenteral dosage forms improve the anticancer pharmacology of the drug. The development of optimized drug delivery systems (DDS) shows promise for the clinical translation of DS into GB adjuvant therapy.

Introduction: In November 2019, the idea of a zoonotic virus crossing over to human transmission in a seafood market in Wuhan, China, and then soaring across the globe to claim over 6.3 million lives and persisting to date, seemed more like wild science fiction than a future reality. As the SARS-CoV-2 pandemic continues, it is important to hallmark the imprints the pandemic has made on science.

Areas covered: This review covers the biology of SARS-CoV-2, vaccine formulations and trials, the concept of 'herd resistance,' and the vaccination divide.

Expert opinion: The SARS-CoV-2 pandemic has changed the landscape of medicine. The rapid approval of SARS-CoV-2 vaccines has changed the culture of drug development and clinical approvals. This change is already leading to more accelerated trials. The RNA vaccines have opened the market for nucleic acid therapies and the applications are limitless - from cancer to influenza. A phenomenon that has occurred is that the low efficacy of current vaccines and the rapid mutation rate of the virus is preventing herd immunity from being attained. Instead, herd resistance is being acquired. Even with future, more effective vaccines, anti-vaccination attitudes will continue to challenge the quest for SARS-CoV-2 herd immunity.

Introduction: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site.

Areas covered: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant.

Expert opinion: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.

Introduction: The incidence of abdominal tumors, such as colorectal and prostate cancers, continually increases. Radiation therapy is widely applied in the clinical treatment of patients with abdominal/pelvic cancers, but it often unfortunately causes radiation enteritis (RE) involving the intestine, colon, and rectum. However, there is a lack of suitable treatment options for effective prevention and treatment of RE.

Areas covered: Conventional clinical drugs for preventing and treating RE are usually applied by enemas and oral administration. Innovative gut-targeted drug delivery systems including hydrogels, microspheres, and nanoparticles are proposed to improve the prevention and curation of RE.

Expert opinion: The prevention and treatment of RE have not attracted sufficient attention in the clinical practice, especially compared to the treatment of tumors, although RE takes patients great pains. Drug delivery to the pathological sites of RE is a huge challenge. The short retention and weak targeting of conventional drug delivery systems affect the therapeutic efficiency of anti-RE drugs. Novel drug delivery systems including hydrogels, microspheres, and nanoparticles can allow drugs long-term retention in the gut and targeting the inflammation sites to alleviate radiation-induced injury.

Introduction: Most lung diseases are serious conditions resulting from genetic and environmental causes associated with high mortality and severe symptoms. Currently, treatments available have a palliative effect and many targets are still considered undruggable. Gene therapy stands as an attractive approach to offering innovative therapeutic solutions. CRISPRCas9 has established a remarkable potential for genome editing with high selectivity to targeted mutations. To ensure high efficacy with minimum systemic exposure, the delivery and administration route are key components that must be investigated.

Areas covered: This review is focused on the delivery of CRISPRCas9 to the lungs, taking advantage of lipid nanoparticles (LNPs), the most clinically advanced nucleic acid carriers. We also aim to highlight the benefits of pulmonary administration as a local delivery route and the use of spray drying to prepare stable nucleic-acid-based dry powder formulations that can overcome multiple lung barriers.

Expert opinion: Exploring the pulmonary administration to deliver CRISPRCas9 loaded in LNPs as a dry powder increases the chances to achieve high efficacy and reduced adverse effects. CRISPRCas9 loaded in LNP-embedded microparticles has not yet been reported in the literature but has the potential to reach and accumulate in target cells in the lung, thus, enhancing overall efficacy and safety.

Introduction: Drugs delivered via the lungs are predominantly used to treat various respiratory disorders, including asthma, chronic obstructive pulmonary diseases, respiratory tract infections and lung cancers, and pulmonary vascular diseases such as pulmonary hypertension. To treat respiratory diseases, targeted, modified or controlled release inhalation formulations are desirable for improved patient compliance and superior therapeutic outcome.

Areas covered: This review summarizes the important factors that have an impact on the inhalable modified release formulation approaches with a focus toward various formulation strategies, including dissolution rate-controlled systems, drug complexes, site-specific delivery, drug-polymer conjugates, and drug-polymer matrix systems, lipid matrix particles, nanosystems, and formulations that can bypass clearance via mucociliary system and alveolar macrophages.

Expert opinion: Inhaled modified release formulations can potentially reduce dosing frequency by extending drug's residence time in the lungs. However, inhalable modified or controlled release drug delivery systems remain unexplored and underdeveloped from the commercialization perspective. This review paper addresses the current state-of-the-art of inhaled controlled release formulations, elaborates on the avenues for developing newer technologies for formulating various drugs with tailored release profiles after inhalational delivery and explains the challenges associated with translational feasibility of modified release inhalable formulations.

Introduction: There has been an active discussion on the sustainability of inhaler therapy in respiratory diseases, and it has cast a shadow on pMDIs which rely on propellant with high global warming potential (GWP). DPIs offer a lower GWP and effective alternative, but there has been concern whether all patients can generate sufficient inspiratory effort to disperse the drug. This review focuses on airflow resistance of DPIs and its clinical relevance.

Areas covered: For this narrative review, we searched the literature for studies comparing flow patterns with different devices. We also included a section on clinical trials comparing reliever administration with DPI, pMDI with spacer, and nebulizer during exacerbation.

Expert opinion: The evidence supports the efficacy of DPIs irrespective of respiratory condition or age of the patient even during acute exacerbations. Air flow resistance does not limit the use of DPIs and the patients were able to generate sufficient inspiratory flow rate with almost any device studied. None of 16 identified clinical trials comparing reliever administration via DPIs to other types of devices during exacerbation or bronchial challenge showed statistically significant difference between the device types in FEV1 recovery. DPIs performed as well as other types of inhaler devices even during asthma or COPD exacerbation.

Introduction: There is a need for investment in manufacturing for vaccine microarray patches (vMAPs) to accelerate vMAP development and access. vMAPs could transform vaccines deployment and reach to everyone, everywhere.

Areas covered: We outline vMAPs' potential benefits for epidemic preparedness and for outreach in low- and lower-middle-income countries (LMICs), share lessons learned from pandemic response, and highlight that investment in manufacturing-at-risk could accelerate vMAP development.

Expert opinion: Pilot manufacturing capabilities are needed to produce clinical trial material and enable emergency response. Funding vMAP manufacturing scale-up in parallel to clinical proof-of-concept studies could accelerate vMAP approval and availability. Incentives could mitigate the risks of establishing multi-vMAP manufacturing facilities early.

Introduction: Mucoadhesive drug delivery systems (MDDS) are specifically designed to interact and bind to the mucosal layer of the epithelium for localized, prolonged, and/or targeted drug delivery. Over the past 4 decades, several dosage forms have been developed for localized as well as systemic drug delivery at different anatomical sites.

Areas covered: The objective of this review is to provide a detailed understanding of the different aspects of MDDS. Part II describes the origin and evolution of MDDS, followed by a discussion of the properties of mucoadhesive polymers. Finally, a synopsis of the different commercial aspects of MDDS, recent advances in the development of MDDS for biologics and COVID-19 as well as future perspectives are provided.

Expert opinion: A review of the past reports and recent advances reveal MDDS as highly versatile, biocompatible, and noninvasive drug delivery systems. The rise in the number of approved biologics, the introduction of newer highly efficient thiomers, as well as the recent advances in the field of nanotechnology have led to several excellent applications of MDDS, which are predicted to grow significantly in the future.