Expert opinion on drug delivery最新文献

Introduction: Delivering drugs to the central nervous system (CNS) remains a major challenge due to the blood-brain barrier, restricting the entry of drugs into the brain. This limitation contributes to the ongoing lack of effective treatments for CNS diseases. To improve the process of drug discovery and development, it is crucial to streamline methods that measure clinically relevant parameters, allowing for good selection of drug candidates.

Area covered: In this paper, we discuss the essential prerequisites for successful CNS drug delivery and review relevant methods. We emphasize the need for closer collaboration between in vitro and in vivo scientists to improve the relevance of these methods and increase the success rate of developing effective CNS therapies. While our focus is on small molecule drugs, we also touch on some aspects of larger molecules.

Expert opinion: Significant progress has been made in recent years in method development and their application. However, there is still work to be done before the use of in silico models, in vitro cell systems, and AI can consistently offer meaningful correlations and relationships to clinical data. This gap is partly due to limited patient data, but a lot can be achieved through in vivo research in animal models.

Introduction: Transdermal patches offer a unique advantage by providing extended therapeutic benefits while maintaining stable plasma drug concentration. The efficacy and safety of patches depend significantly on their ability to adhere to the skin, a feature influenced by various external and internal factors.

Areas covered: The review primarily focuses on the fundamental aspects of adhesion in transdermal patches, including basic information about the skin, the underlying principles of adhesion, drug delivery, and adhesion characteristics of pressure sensitive adhesives (PSAs), adhesion issues, impact factors, strategies to improve patch adhesion, and relevant molecular mechanisms.

Expert opinion: The development of transdermal patches with sufficient adhesion for consistent and extended drug delivery remains a challenging task. Challenges in adhesion stem from the complex interplay among PSAs, permeation enhancers, active pharmaceutical ingredients (APIs), and other excipients in current patch compositions, further complicated by variations arising from dermatological factors. These intricacies significantly impede the consistent effectiveness of patches. Progress in the exploration of new PSA polymers, in conjunction with innovative patch compositions, is crucial for establishing an optimal equilibrium between drug utilization rate, drug-loading, drug release, and adhesion, thus effectively addressing the challenges related to adhesion.

Introduction: Cyclic antimicrobial peptides (CAMPs) are gaining attention as promising candidates in advanced drug delivery systems due to their structural stability, resistance to proteolytic degradation, and versatile therapeutic potential. Their unique properties enable applications that extend beyond combating multidrug-resistant (MDR) pathogens. Their amphipathic and cell-penetrating properties allow them to efficiently transport drugs across cellular membranes.

Areas covered: This review explores the structural advantages and mechanisms of action of CAMPs, emphasizing their role in drug delivery. The literature analysis (2010-2024) from PubMed, Scopus, and Web of Science highlights developments in CAMP-conjugated therapies, liposomal formulations, and encapsulation systems. The review also examines their antimicrobial potency, amphipathic and cell-penetrating properties, and integration into nanocarrier technologies to enhance drug stability, bioavailability, and precision targeting. Challenges such as toxicity, scalability, and cost are also discussed. CAMPs have the potential to revolutionize drug delivery through their robustness and multifunctionality, particularly in precision medicine.

Expert opinion: Future advancements in peptide engineering, nanotechnology, and AI-driven design are expected to enhance CAMPs' therapeutic specificity, reduce toxicity, and broaden their applications, including oncology and gene therapy, paving the way for their integration into next-generation therapeutics.

Introduction: Androgenic alopecia is a multifactorial disease with a high incidence and a great psychological burden on patients. The current FDA-approved treatment is topical minoxidil or oral finasteride. However, both present significant limitations. While the systemic absorption of finasteride causes serious sexual side effects, minoxidil's low solubility imposes a challenge in obtaining a non-irritative and effective formulation. One way to solve such limitations is by using nanocarriers targeting the drug delivery to the hair follicles upon topical application.

Areas covered: Here, we review which advancements have been made to achieve a more effective treatment for androgenic alopecia, focusing on nanocarriers for the topical drug delivery systems developed to target hair follicles.

Expert opinion: The results from multiple reviewed studies demonstrate the potential of incorporating drugs into different nanocarriers to improve follicular targeting in drug delivery for androgenic alopecia treatment. However, many studies fail to perform the proper controls. Most studies also do not quantify the drug accumulation in all skin layers, especially in hair follicles, which avoids comparisons between different nanocarriers and, hence, reliable conclusions. Future experiments with a broader nanocarrier size range, suitable skin models and controls, and clinical tests to assess the safety of developed formulations will improve the androgenic alopecia treatment.

Introduction: Although there are numerous options for epilepsy treatment, its effective control continues unsatisfactory. Thus, search for alternative therapeutic options to improve the efficacy/safety binomial of drugs becomes very attractive to investigate. In this context, intranasal administration of antiseizure drugs formulated on state-of-the-art nanosystems can be a promising strategy.

Areas covered: This work gives a comprehensive overview of different intranasal nanosystems for antiseizure drug administration developed and evaluated on preclinical studies over the last 10 years and published in 'PubMed' and 'Web of Science' databases. Additionally, it highlights their pharmaceutical critical quality attributes and in vivo pharmacological outputs that might infer possible results when transposing to clinical trials.

Expert opinion: Research into optimized nanosystems encapsulating antiseizure drugs to enhance direct nose-to-brain delivery has increased over the last years. Particularly, the interest in formulating first- and second-generation antiseizure drugs in nanoparticles is here highlighted, having demonstrated its in vivo safety and improvement on pharmacokinetic and efficacy outputs. Still, none of them were brought to clinical trials. Thus, considering the existing barriers between preclinical and clinical trials, if supported by robust and targeted quality by design approaches, intranasal drug delivery can be presented as a valid and superior alternative for epilepsy treatment.

Introduction: Chronic non-healing wounds have emerged as a significant global healthcare challenge. Biofilm induced wound infections has been widely acknowledged. Despite the advanced understanding of biofilm formation, the existing approaches for diagnosing biofilms in wounds remain considerably suboptimal. Chemical signals produced by fungi to sense their environment, known as quorum sensing (QS) molecules are anticipated to cause revolution in non-healing wound antisepsis.

Areas covered: Biofilms render chronic wounds resistant to treatment and impede tissue repair by inducing chronic inflammation. QS is a biochemical signaling pathway that involves certain secreted molecules, namely phenylethanoids, indolyl, and sesquiterpene alcohols that can significantly minimize and obliterate bacterial biofilms if properly applied and released in wound treatments.

Expert opinion: QS molecules (QSMs) possess inhibitory properties that obstruct the formation of microbial biofilms and exhibit synergism with common antimicrobials. They can disrupt biofilms formed by drug-resistant microorganisms. The understanding of the current mechanisms and advancements in the utilization of QSMs within diverse drug delivery systems, and their release dynamics will be crucial in new drug design and delivery. Exploration of co-delivery of drugs alongside QS molecules, and assessing their impact on healing of chronic wounds before moving to clinical trials remain unaddressed.

Introduction: mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, in vivo chimericantigen receptor T  (CAR T) celltherapies and protein replacement.  mRNAis large, charged, and easily degraded by nucleases. It cannot get into cells,escape the endosome, and be translated to a disease-modifying protein without adelivery system such as lipid nanoparticles (LNPs).

Areas covered: This article covers how to design, select, and develop an LNP fortherapeutic genome editing in the liver. The roadmap is divided into selectingthe right LNP in discovery via a design, make, test, analyze cycle (DMTA). Thedesign elements are focused on the ionizable lipid in a 4-component LNP, andinsights are provided for how to set an invitro and in vivo testingstrategy. The second section focuses on transforming the LNP into a clinicaldrug product and covers formulation, analytical development and processoptimization, with brief notes on supply and regulator strategies.

Expert opinion: The perspective discusses the impact thatacademic-industry collaborations can have on developing new medicine fortherapeutic genome editing in the liver. From the cited collaborations an enhancedunderstanding of intracellular trafficking, notably endosomal escape, and theinternal structure of LNPs were attained and are deemed key to designingeffective and safe LNPs. The knowledge gained will also enable additional assays and structure activity relationships, which wouldlead to the design of the next generation delivery systems for nucleic acidtherapies.

Introduction: Liposomal hydrogels are novel drug delivery systems that comprise preformed liposomes incorporated in hydrogels destined for mostly localized drug therapy, herewith antimicrobial therapy. The formulation benefits from versatility of liposomes as lipid-based nanocarriers that enable delivery of various antimicrobials of different lipophilicities, and secondary vehicle, hydrogel, that assures better retention time of formulation at the infection site. Especially in an era of alarming antimicrobial resistance, efficient localized antimicrobial therapy that avoids systemic exposure of antimicrobial and related side effects is crucial.

Areas covered: We provide an overview of liposomal hydrogels that were developed for superior delivery of antimicrobials at different infections sites, with focus on skin and vaginal infections. The review summarizes the challenges of infection site and most common infection-causing pathogens and offers commentary on most relevant features the formulation needs to optimize to increase the therapy outcome. We discuss the impact of liposomal composition, size, and choice of polymer-forming hydrogel on antimicrobial outcome based on the literature overview and own experience in the field.

Expert opinion: Liposomal hydrogels offer improved therapy outcome in localized antimicrobial therapy. By fine-tuning of liposomal as well as hydrogel properties, formulations with superior performance can be optimized targeting specific infection site.