INTRODUCTION:Polyendocrine Metabolic Ovarian Syndrome (PMOS) is an endocrine disorder characterized by metabolic dysfunction, hormonal imbalance, inflammation, and clinical manifestations. Current treatments, systemic drugs, may provide limited benefits because of adverse effects, variable efficacy, and poor adherence, highlighting the need for personalized therapeutic strategies. Vaginal administration offers an underexplored approach that may enable localized delivery, reduce systemic exposure, and dosing frequency. Furthermore, the vaginal microenvironment can influence drug stability, absorption, retention, and therapeutic outcomes. AREAS COVERED:This review examines the pathophysiological basis of PMOS and recent advances in vaginal drug delivery (VDD) systems for precision therapy. It highlights the transition from conventional approaches to nanoscale carriers, bioresponsive formulations, genetic and microbiome-informed strategies, and 3D-printed devices. The roles of artificial intelligence, machine learning, point-of-care diagnostics, and theranostic platforms in personalized therapy are discussed, together with translational and regulatory considerations. Relevant literature was compiled by searching PubMed, Scopus, Web of Science, and Google Scholar. EXPERT OPINION:VDD represents a promising precision medicine approach for PMOS; however, clinical translation remains challenged by vaginal microenvironment variability, limited safety evidence, formulation scalability, patient acceptance, and insufficient clinical validation. Future progress will require interdisciplinary integration of biomaterial engineering, biology, drug delivery, microbiome science, and digital health.
INTRODUCTION:The reduced diversity of the lung microbiome in respiratory conditions, including bronchiectasis, promotes bacterial infection and inflammation, contributing to worsening clinical outcomes. Traditional treatments often fail to address both infection and inflammation. Because of their potential dual-action, lactic acid bacteria (LAB) directly administered to the lungs could represent an innovative therapeutic approach for these diseases. RESEARCH DESIGN AND METHODS:Two powders for inhalation containing Lpb. plantarum, lactose, l-leucine with and without raffinose, a prebiotic, were produced by spray drying and in vitro tested. The focus was on investigating their potential in vitro anti-inflammatory and anti-microbial activities against S. aureus. RESULTS:The powders showed a fine particle fraction (<5 µm) >40% and allowed to maintain anti-inflammatory activity in vitro for both treatment and prevention. Moreover, both the powders led to a significant reduction in S. aureus growth. The stability study of the powders in capsules at different storage conditions showed the preservation of the LAB up to 90 days in refrigerated conditions (4°C/-20°C). CONCLUSIONS:This proof-of-concept study shows that inhalable spray-dried live LABs retain biological activity and are suitable for pulmonary delivery, supporting their potential as a microbiota-modulating therapy which, however, requires further preclinical validation.
INTRODUCTION:Nutraceuticals have garnered increasing scientific and commercial interest for their potential roles in health promotion, disease prevention and adjunctive disease management. However, the complex physicochemical and biological environment of the gastrointestinal (GI) tract presents formidable barriers to their effective oral delivery, contributing to a persistent gap between preclinical promise and clinical efficacy. A mechanistic understanding of GI physiology, nutraceutical-specific delivery challenges and available formulation strategies is therefore essential to advance the field. AREAS COVERED:Preclinical and clinical studies exploring the oral delivery of nutraceuticals were identified through targeted PubMed, Scopus and Web of Science searches to examine the GI tract as a dynamic delivery environment. Nutraceuticals are classified according to their primary delivery challenges, including lipophilicity, chemical and enzymatic lability and requirements for colon-targeted or microbiome-directed delivery. Formulation strategies are reviewed mechanistically, with particular attention to lipid-based systems, polymeric nanoparticles, hydrogel and hybrid biomaterials and colon-targeted delivery platforms. EXPERT OPINION:Advancing nutraceutical science requires moving toward a formulation-driven approach to overcome the biological barriers faced by oral delivery. There is a critical need for regulatory oversight to ensure that marketed claims are backed by scientific evidence relating to nutraceutical pharmacokinetics, pharmacodynamics and safety evaluations.
INTRODUCTION:Immunoliposomes (ILs) allow selective interaction with cells by antibodies or their fragments. When associated with superparamagnetic iron oxide nanoparticles (SPIONs), they form immunomagnetoliposomes (IMLs) that enable targeting, drug-release triggers, thermal ablation, and imaging, allowing real-time observation, therapy response, and patient stratification. AREAS COVERED:This study is about the development and application of antibody and fragment conjugates in SPION-loaded liposomes as a multifunctional platform to overcome the disadvantages of conventional therapies for breast cancer (BC), including an overview of clinical trials with ILs and the prospects for IMLs. The databases searched include PubMed, Scopus, Google Scholar, Clinicaltrials.gov, and reports by regulatory agencies, focusing on articles from the period 2015-2026. EXPERT OPINION:IML's advantages do not represent a definitive solution but may partially mitigate the uncertainties associated with BC therapy. Its impact consists of its ability to enable clinical therapies in a controlled, monitored manner. The clinical failures of two of three clinical trials involving antibody-directed liposomes (NCT02833766 and NCT02213744) demonstrate the need for IMLs as versatile systems that more effectively overcome the therapeutic limitations of accumulation and penetration in solid tumors associated with ILs.
INTRODUCTION:Microneedles (MNs) have emerged as a versatile platform for transdermal delivery, enabling minimally invasive administration of small molecules and biologics. As their performance is fundamentally determined by material properties, continuous innovation in MN materials has been central to the evolution of the field. AREAS COVERED:Relevant literature published from 2020 to 2026 is surveyed using Web of Science and PubMed. This review analyzes MN materials using a functional paradigm framework covering structural carriers, controlled-release carriers, intelligent integrated carriers, and emerging all-drug glassy systems. It compares representative materials by design rationale, advantages, limitations, and trade-offs among drug loading, release control, and biocompatibility, and highlights recent advances together with major challenges to clinical translation. EXPERT OPINION:Current progress suggests that MN material design is shifting from proof-of-concept innovation toward translation-oriented optimization. Increasing functionality alone is unlikely to ensure clinical impact unless it is accompanied by reproducibility, manufacturability, safety, and application-specific performance. Future advances will likely depend on simplified high-performance material systems, more predictable responsive release, and drug-specific designs that better balance loading capacity, release precision, and biocompatibility.
INTRODUCTION:Nasal administration provides a favorable option for patients with a variety of disease conditions and their caregivers, including for acute treatment therapies in the community setting. This noninvasive route of administration allows for device portability and quick access, absorption, and bioavailability. Drug products should be developed with an understanding of ideal formulation characteristics and device criteria to ensure high bioavailability, effectiveness, and tolerability. AREAS COVERED:This narrative review examines how intranasal administration addresses limitations associated with some other routes of administration and how its unique limitations can be addressed. There are numerous strategies to increase mucosal absorption, such as mucoadhesion and permeation enhancement. PubMed was searched for excipient dodecyl maltoside (DDM) in transmucosal absorption; those results were used for subsequent research. We discuss DDM use in formulations approved by several health authorities worldwide, including the US Food and Drug Administration, and in investigational drugs. EXPERT OPINION:DDM has demonstrated benefits in enhancing absorption in nasal spray formulations across a broad spectrum of medical conditions. These new treatment options offer effectiveness and ease of use for patients and caregivers. DDM and closely related excipients have many promising opportunities for future applications, facilitating absorption across nasal and other epithelial membranes.
INTRODUCTION:Breast cancer remains a leading cause of mortality among women worldwide, with diagnoses projected to reach 3.5 million annually by 2050. Therapeutic progress is hindered by marked molecular heterogeneity and distinct biological and clinical subtypes. Antibody-drug conjugates (ADCs) have emerged as a promising strategy for treatment‑resistant disease, combining targeted delivery with potent cytotoxic payloads. AREAS COVERED:This review synthesizes literature spanning 1990-2026 on advances in ADC design and their clinical and translational implementation in breast cancer. Primary research articles were then inputted into Research Rabbit to identify additional original research articles and maximize data retrieval. EXPERT OPINION:The success of ADCs is limited less by payload potency than by delivery biology. Efficacy depends on patient context, tumor site-specific factors, and bystander effects in antigen‑heterogeneous environments. However, current development often overlooks systemic antigen sinks, metastatic microenvironments, and evolving resistance. Traditional ADCs rely on a narrow range of tumor antigens and payloads, restricting therapeutic index and applicability. Future progress requires reframing antigen selection as a system-level challenge, supported by delivery-focused engineering, precision-medicine-driven trial design, and adaptive methodology.
INTRODUCTION:Atopic dermatitis (AD) is a recurring and non-contiguous dermatological condition that impacts a huge global population. Pruritus, inflammation, numerous eczematous lesions, and an unpredictable progression are the hallmark characteristics of this dermatological complication. Despite its multifactorial and incompletely comprehended pathophysiology, AD appears from a combined cause of environmental and genetic factors that lead to epidermal barrier integrity, oxidative stress, and immune system imbalance at both the skin and systemic levels. AREAS COVERED:The lipid nanocarrier (LN), referred to as the vesicular system, has become a focal point of interest among researchers striving to develop novel formulations that improve therapeutic efficacy, avoid off-target effects, prevent premature drug degradation, and increase the safety profile of drugs by different surface modification methods. Hence, LNs are categorized into hard-LNs with hardened surfaces and soft-LNs that can alter their size during distribution in the body for delivering both lipophilic and hydrophilic drugs topically. EXPERT OPINION:In the last two decades, numerous clinical studies have clearly shown the therapeutic relevance of specialized LNs and hybrid systems for effectively managing AD and halting its progression with improved quality of patient life, supporting the therapeutic superiority of advanced LN-mediated interventions compared to traditional treatment modalities.
INTRODUCTION:Appropriate dry powder inhaler (DPI) selection is essential for effective COPD management because pulmonary drug delivery depends on interactions between formulation properties, device design, and patient capability. This review proposes a Formulation-Device-Patient (FDP) matching framework to support individualized DPI selection. AREAS COVERED:A structured search of PubMed and Google Scholar identified publications on COPD, DPI selection, inspiratory flow, device resistance, aerosol performance, inhaler technique, usability, and formulation-device interactions. Evidence shows that DPIs differ substantially in internal resistance, inspiratory-flow requirements, dose-preparation mechanisms, aerosolization characteristics, handling complexity, and feedback systems, and therefore should not be considered interchangeable. Appropriate device selection requires assessment of inspiratory capability alongside manual dexterity, cognitive function, comorbidities, prior inhaler experience, patient preference, and inhaler technique. The review also highlights the limitations of direct cross-device comparisons and cautions against interpreting in vitro aerosol-performance metrics as indicators of clinical superiority. EXPERT OPINION:DPI selection should move beyond device-centered prescribing toward individualized formulation-device-patient matching. The proposed FDP framework provides a practical model for individualized DPI selection by integrating formulation characteristics, device engineering, and patient capability rather than relying on inspiratory flow or device characteristics alone.
INTRODUCTION:Breast cancer is the most common cancer diagnosed globally, with various levels of heterogeneity. The current treatment strategy for breast cancer includes surgery, chemotherapy, radiation, hormone, targeted, and immunotherapy. These strategies are combined according to the stage, patient factors, and molecular subtype of breast cancer to enhance survival and diminish the recurrence of cases. Several adverse effects and challenges are associated with these therapies, which render the patient uncomfortable and non-compliant. AREAS COVERED:Bioconjugate-based therapy is one of the advanced therapies emerging to diagnose and treat breast cancer, in which conjugation is done between various molecules, such as monoclonal antibodies and cytotoxic drugs, radionuclides, enzymes, polymers, ligands, and nanoparticles, using linkers. This review aims to critically discuss bioconjugate's recent research advancements in breast cancer theranostics, highlighting their strengths and gaps toward clinical translation, along with patents and clinical trials. PubMed, Scopus, and Google Scholar were used to search the literature in the last five years (2021 to present). EXPERT OPINION:The outcomes of the findings are promising; however, more studies need to be done to establish the mechanistic pathway, long-term toxicity, safety, efficacy, and stability of the bioconjugates for breast cancer to move toward clinical settings.
INTRODUCTION:Chronic wound infections remain a major healthcare challenge due to persistent polymicrobial biofilms and the increasing prevalence of antimicrobial resistance. Conventional antimicrobial therapies often fail to eradicate biofilms, highlighting the need for innovative therapeutic strategies. Metal complexes have emerged as promising candidates owing to their multitarget antimicrobial and antibiofilm activities and potential for localize wound treatment. AREAS COVERED:This review examines the role of metal complexes in combating biofilm-associated wound infections. Their mechanisms of action, including membrane disruption, redox imbalance, quorum-sensing inhibition, metabolic interference, and biofilm matrix destabilization, are discussed. The review further explores the integration of metal complexes into advanced transdermal and wound patch platforms, including polymeric matrices, nanocomposite systems and stimuli-responsive delivery systems designed to enhance localized drug release, improve wound retention, and minimize systemic toxicity. Current preclinical and translational developments are also highlighted. EXPERT OPINION:Metal-complex-based transdermal therapeutics represent a promising next-generation approach for managing chronic biofilm-mediated wound infections and overcoming antimicrobial resistance. However, successful clinical translation requires addressing challenges related to toxicity, formulation stability, manufacturing scalability, regulatory approval, and long-term safety. Future interdisciplinary efforts integrating microbiology, materials science, and clinical research will be essential to advance these technologies from laboratory to clinical practice.
INTRODUCTION:Proteolysis-targeting chimeras (PROTAC) are an innovative treatment approach that selectively breaks down disease-relevant proteins by utilizing the ubiquitin-proteasome system. Other than PROTAC, Molecular glue, Lysosome-Targeting Chimaera (LYTAC), GlueTAC, Autophagy-Targeting Chimaera (AUTAC), Autophagosome Tethering Compound (ATTEC), and Antibody-based PROTAC (AbTAC) are emerging targeted protein degradation (TPD) techniques, of which PROTAC offers several benefits. AREAS COVERED:This review discusses the development of proteolysis-targeting chimeras (PROTACs) for targeted protein degradation, highlighting their mechanism of action via the ubiquitin-proteasome system. It examines key physicochemical and pharmacokinetic challenges that limit clinical translation. Advanced formulation strategies, including nanoformulations and amorphous solid dispersions, prodrug improve solubility, bioavailability, and therapeutic efficacy. Additionally, characterization techniques are summarized, and the review outlines recent progress and critical considerations for the successful clinical translation of PROTAC-based therapeutics. Relevant articles from PubMed, Scopus, and Web of Science, spanning publications up to 2026, were gathered. EXPERT OPINION:PROTACs represent a transformative therapeutic modality, enabling selective protein degradation beyond conventional inhibition. Future research should focus on improving bioavailability, targeted delivery, and stability, while advancing prodrug strategies, E3 ubiquitin ligase selectivity, oral formulations, and predictive models for clinical translation. Additionally, it should emphasize scalable manufacturing, regulatory frameworks, and integration with emerging targeted protein degradation technologies.
Introduction Macromolecular and nanoparticulate drug carriers are increasingly important in oncology due to improved targeting and reduced systemic toxicity; however, their delivery to solid tumors is often limited by size-dependent transport barriers.Methods We present a computational modeling framework that couples microvascular blood flow, transvascular exchange, interstitial fluid flow, and macromolecule transport to investigate the interplay between drug properties, particularly particle size, and tumor capillary structural characteristics. A stochastic capillary network generation algorithm was developed to produce realistic microvascular networks with heterogeneous vessel radius, branching patterns, and permeability properties.Results Simulations show an inverse relationship between particle size and penetration and quantify how pore radius and pore area fraction modulate extravasation and tissue dispersion.Conclusions Overall, the framework may serve as a prototype in silico tool for drug formulation design, supporting the selection of molecular formats and sizes that distribute more efficiently within tumors under tumor-specific biophysical constraints.
INTRODUCTION:The advent of liposomal amphotericin B (L-AmB, commercialized as AmBisome) technology represented a paradigm shift in antifungal drug delivery, substantially reducing the severe, well-known nephrotoxicity historically associated with the conventional deoxycholate formulation (D-AmB). Despite this advance, the expiration of the innovator's patent has spurred the global development of generic liposomal preparations, raising critical biopharmaceutical and clinical safety concerns. AREAS COVERED:This article reviews the literature and regulatory landscape of L-AmB and its nanosimilars. A comprehensive search was performed using PubMed, Embase, and Web of Science (1990-2026), focusing on NBCDs, bioequivalence, and clinical safety. The scope includes an evaluation of marketed generic formulations, their regulatory registrations, and published comparative studies. We also discuss the clinical consequences of administering unstable generics during high-dose protocols. EXPERT OPINION:While recognizing the urgent need for affordable generic alternatives to democratize access in low- and middle-income countries (LMICs), we emphasize the necessity of stringent, internationally harmonized regulatory standards that go beyond conventional bioequivalence. Safeguarding biopharmaceutical fidelity is an indispensable clinical imperative to protect vulnerable patients from the severe hidden costs of therapeutic failure and drug-induced toxicity.
INTRODUCTION:Oral mucositis (OM) remains a common and clinically significant complication of chemotherapy and radiotherapy. Current management is largely supportive, and effective local therapies remain limited. Hydrogel-based delivery systems have attracted interest because they may improve mucosal retention, protect ulcerated tissue, and enable sustained local drug release. METHODS:A systematic review of preclinical animal studies evaluating hydrogel-based interventions for oral mucositis was conducted. PubMed, Embase, and the Cochrane Library were searched, with additional gray literature screening. Data on formulation characteristics, experimental models, therapeutic outcomes, and methodological quality were extracted. Risk of bias was assessed using the SYRCLE tool. RESULTS:Eighteen studies met the inclusion criteria. Most formulations reduced lesion severity, improved histological healing, and attenuated inflammatory or oxidative markers. Multifunctional systems combining mucoadhesion with anti-inflammatory, antioxidant, or antimicrobial activity tended to show broader effects than conventional gels. However, study design, outcome reporting, and translational endpoints were heterogeneous. CONCLUSIONS:Current preclinical evidence supports hydrogels as promising local drug delivery platforms for oral mucositis. Greater standardization of models and clinically relevant endpoints will be important to support translation into human studies. PROTOCOL REGISTRATION:https://www.crd.york.ac.uk/prospero/, identifier CRD420251072050.
INTRODUCTION:A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. AREAS COVERED:This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. EXPERT OPINION:Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake.
INTRODUCTION:Breast cancer (BC) remains one of the most prevalent malignancies worldwide, characterized by molecular heterogeneity, therapeutic resistance, and high recurrence rates that limit the success of conventional treatments. Although chemotherapy and targeted therapies have improved patient outcomes, their effectiveness is often compromised by off-target toxicity, poor tumor selectivity, and multidrug resistance. Liposomal nanocarriers improves drug stability and circulation while enhancing passive tumor accumulation via the EPR effect. However, conventional liposomes exhibit limited cellular internalization and inadequate tumor penetration. AREA COVERED:This review discusses ligand-functionalized liposomes for active targeting in BC. Surface modification with antibodies, peptides, aptamers, carbohydrates, and small molecules enables selective binding to overexpressed receptors, improving cellular uptake and intracellular drug delivery. The literature was screened using PubMed, ScienceDirect, Google Scholar, and Scopus. Recent advances in multifunctional systems, including dual-targeting strategies, stimuli-responsive release mechanisms, and combination therapies, are also examined. CONCLUSION:Ligand-modified liposomes show strong potential to enhance therapeutic precision, pharmacokinetics, and safety. These have the potential of targeted delivery, decreased toxicity, and improved therapeutic effects. However, challenges such as tumor heterogeneity, large-scale manufacturing, and regulatory constraints must be addressed for successful clinical translation.
INTRODUCTION:Despite over three-decades of work, no inhalable nucleic acid delivery system for cystic fibrosis (CF) has advanced beyond Phase II due to a lack of congruence between positive outcomes from in vitro and preclinical work, and lung function improvements in people with CF. AREAS COVERED:We review publications covering in vitro and in vivo animal models for CF research from databases including Web of Science and PubMed. Data were used to evaluate the performance of inhaled nucleic acid delivery systems for CF and examine why positive outcomes in these models fail to predict clinical responses. EXPERT OPINION:The field should recalibrate expectations regarding the proportion of epithelial cell correction required for meaningful clinical improvement since the threshold for sustained improvement in lung function in humans may be substantially higher. No single model can predict clinical responses. Translation robustness depends on integrating multiple systems that collectively interrogate delivery, persistence, safety and functional restoration of lung function in clinically meaningful settings. Appropriate in vitro air-liquid interface models that accurately recapitulate the CF airways are important starting points, followed by delivery and functional evaluation in CF animal models that closely resemble human lung physiology and disease phenotype, including pigs and ferrets.
INTRODUCTION:Breast cancer remains the most prevalent malignancy among women worldwide, with its pronounced molecular heterogeneity demanding therapeutic strategies that transcend conventional systemic chemotherapy toward tumor-selective, molecularly precise interventions. The convergence of biomarker science, engineered nanomedicine, and artificial intelligence (AI) offers a transformative framework for realizing this goal. AREAS COVERED:This review examines how molecular biomarkers (e.g. mucin glycoproteins, human epidermal growth factor receptor 2 (HER2), circulating tumor cells, and circulating tumor DNA) serve dual roles as diagnostic identifiers and active targeting ligands directing engineered nanocarriers. We critically evaluate biomarker-guided nanoplatforms (liposomal, polymeric, metallic, and protein-based architectures), stimuli-responsive drug release strategies, and AI-driven microfluidic manufacturing for scalable, good manufacturing practice-compliant nanoparticle production. Literature was retrieved from PubMed/MEDLINE, Scopus, and Web of Science (2000-2026), supplemented by ClinicalTrials.gov data. EXPERT OPINION:Near-term clinical impact is most realistically achieved through AI-assisted biomarker interpretation and multi-analyte liquid biopsy integration rather than novel nanoformulations, whose translational attrition remains high. Bridging the bench-to-bedside gap requires prospective biomarker-stratified clinical trials, co-developed companion diagnostics, and federated AI architectures as advances that will progressively replace static histological subtype classification with a continuously updated, molecularly individualized treatment paradigm for breast cancer.
