Expert Opinion on Drug Delivery

INTRODUCTION: Photodynamic therapy (PDT) has gained significant attention due to its superiority over conventional treatments. In the context of skin cancers and nonmalignant skin diseases, topical application of photosensitizer formulations onto affected skin, followed by illumination, offers distinct advantages. Topical PDT simplifies therapy by providing easy access to the skin, increasing drug concentration within the target area, and confining residual photosensitivity to the treated skin...

INTRODUCTION: Triple-negative breast cancer (TNBC) presents unique challenges indiagnosis and treatment.Resveratrolexhibits potential as a therapeutic intervention for TNBC byregulating various pathways such as the PI3K/AKT, RAS/RAF/ERK, PKCδ,and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to itspoor biopharmaceutical characteristics and low bioavailability at thetumor site...

INTRODUCTION: Polymer-lipid hybrid nanoparticle (PLN) is an emerging nanoplatform with distinct properties and functionalities from other nanocarrier systems. PLN can be optimized to overcome various levels of drug delivery barriers to achieve desired therapeutic outcomes via rational selection of polymer and lipid combinations based on a thorough understanding of their properties and interactions with therapeutic agents and biological systems. AREAS COVERED: This review provides an overview of PLN including the motive and history of PLN development, types of PLN, preparation methods, attestations of their versatility, and design strategies to circumvent various barriers for increasing drug delivery accuracy and efficiency...

INTRODUCTION: Transdermal delivery has been extensively investigated as a successful alternative to the oral and parenteral routes of administration. The use of polymeric nanoparticles as drug delivery systems through this route has always been controversial. The use of meta-analyses is a useful quantitative means to decide upon the efficiency of this type of vehicles transporting drugs through the skin. AREAS COVERED: In this meta-analysis study, polymeric nanoparticles were quantitatively compared to conventional formulations in order to investigate the feasibility of using these particles in transdermal delivery...

BACKGROUND: This study aimed to confirm that the incremental dose/clicks system dispenses accurate doses for the Merck family of fertility pen injectors. RESEARCH DESIGN AND METHODS: Set doses (Vset ) for three dose dial settings (minimum dose [Vmin ], midpoint dose [Vmid ] and maximum dose [Vmax ] for the follitropin alfa, choriogonadotropin alfa [D2 classification: single use/variable dose], and follitropin alfa:lutropin-alfa 2:1 combination pen injectors) or a single Vset for the choriogonadotropin alfa (D1 classification: single use/single dose) were assessed...

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms...

INTRODUCTION: The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs...

INTRODUCTION: Using engineered exosomes produced from stem cells is an experimental therapeutic approach for treating brain diseases. According to reports, preclinical research has demonstrated notable neurogenesis and angiogenesis effects using modified stem cell-derived exosomes. These biological nanoparticles have a variety of anti-apoptotic, anti-inflammatory, and antioxidant properties that make them very promising for treating nervous system disorders. AREAS COVERED: This review examines different ways to enhance the delivery of modified stem cell-derived exosomes, how they infiltrate the blood-brain barrier (BBB), and how they facilitate their access to the brain...

OBJECTIVES: Nanomedicines are being actively developed as inhalable drug delivery systems. However, there is a distinct utility in developing smaller polymeric systems that can bind albumin in the lungs. We therefore examined the pulmonary pharmacokinetic behavior of a series of lipidated brush-PEG (5 kDa) polymers conjugated to 1C2 , 1C12 lipid or 2C12 lipids. METHODS: The pulmonary pharmacokinetics, patterns of lung clearance and safety of polymers were examined in rats...

INTRODUCTION: Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues associated with its delivery including poor solubility and bioavailability, instability in acidic media, poor intestinal permeability, dose and aggregation state dependent toxicity, parenteral administration, and requirement of cold chain for transport and storage etc. AREAS COVERED: Scientists have formulated and explored various covalent conjugates of AmB to reduce its toxicity with increase in solubility, oral bioavailability, and payload or loading of AmB by using various polymers, lipids, carbon based nanocarriers, metallic nanoparticles, and vesicular carriers etc...

INTRODUCTION: The Food and Drug Administration's approval of the first three-dimensional (3D) printed tablet, Spritam®, led to a burgeoning interest in using 3D printing to fabricate numerous drug delivery systems for different routes of administration. The high degree of manufacturing flexibility achieved through 3D printing facilitates the preparation of dosage forms with many actives with complex and tailored release profiles that can address individual patient needs. AREAS COVERED: This comprehensive review provides an in-depth look into the several 3D printing technologies currently utilized in pharmaceutical research...

INTRODUCTION: Exosomes, a type of extracellular vesicles, are effective tools for delivering small-molecule drugs and biological therapeutics into cells and tissues. Surface modifications with targeting ligands ensure precise delivery to specific cells, minimizing accumulation in healthy organs and reducing the side effects. This is a rapidly growing area in drug delivery research and this review aims to comprehensively discuss the recent advances in the field. AREA COVERED: Recent studies have presented compelling evidence supporting the application of exosomes as efficient delivery vehicles that escape endosome trapping, achieving effective in vivo delivery in animal models...

BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the E×4formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified E×4(Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process...

INTRODUCTION: Successful neuropharmacology requires optimization of CNS drug delivery and, by extension, free drug concentrations at brain molecular targets. Detailed assessment of blood-brain barrier (BBB) physiological characteristics is necessary to achieve this goal. The 'next frontier' in CNS drug delivery is targeting BBB uptake transporters, an approach that requires evaluation of brain endothelial cell transport processes so that effective drug accumulation and improved therapeutic efficacy can occur...

INTRODUCTION: Tuberculosis (TB) is a global health problem that poses a challenge to global treatment programs. Rifampicin is a potent and highly effective drug for TB treatment; however, higher oral doses than the standard dose (10 mg/kg/day) rifampicin may offer better efficacy in TB treatment. AREAS COVERED: High oral dose rifampicin is not implemented in anti-TB regimens yet and requires about a 3-fold increase in dose for increased efficacy. We discuss inhaled delivery of rifampicin as an alternative or adjunct to oral high dose rifampicin...

INTRODUCTION: Intravesical drug delivery (IDD) has gained recognition as a viable approach for treating bladder-related diseases over the years. However, it comes with its set of challenges, including voiding difficulties and limitations in mucosal and epithelial penetration. These challenges lead to drug dilution and clearance, resulting in poor efficacy. Various strategies for drug delivery have been devised to overcome these issues, all aimed at optimizing drug delivery. Nevertheless, there has been minimal translation to clinical settings...

INTRODUCTION: Tackling low water solubility of drug candidates is a major challenge in today's pharmaceutics/biopharmaceutics, especially by means of modern solubility-enabling formulations. However, drug absorption from these formulations oftentimes remains unchanged or even decreases, despite substantial solubility enhancement. AREAS COVERED: In this article we overview the simultaneous effects of the formulation on the solubility and the apparent permeability of the drug, and analyze the contribution of this solubility-permeability interplay to the success/failure of the formulation to increase the overall absorption and bioavailability...

INTRODUCTION: Due to the concerns raised by the extensive application of PEGylation, polypeptides have stood out as excellent candidates with adequate biocompatibility and biodegradability with tunable hydrophilicity. AREAS COVERED: In this review, polypeptides with the potential to replace PEGylation have been summarized and their application has been reviewed, including XTEN, PASylation, polysarcosine, zwitterion polypeptides, ELPylation, etc. Besides their strengths, the remaining challenges have also been discussed and the future perspectives have been provided...

OBJECTIVES: A profound comprehension of the molecular mechanisms underpinning the enantioselective transdermal permeation of chiral drugs is critical in the design and assessment of transdermal preparations. The primary objective of this study is to investigate the distinct skin permeation behaviors exhibited by enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs) and elucidate the intricate molecular mechanism at play. METHODS: In vitro and in vivo transdermal permeation studies of chiral NSAIDs were performed using transdermal patch and solution system...

INTRODUCTION: The efficiency of brain therapeutics is greatly hindered by the blood-brain barrier (BBB). BBB's protective function, selective permeability, and dynamic functionality maintain the harmony between the brain and peripheral region. Thus, the design of any novel drug carrier system requires the complete study and investigation of BBB permeability, efflux transport, and the effect of associated cellular and non-vascular unit trafficking on BBB penetrability. The in vitro BBB models offer a most promising, and reliable mode of initial investigation of BBB permeability and associated factors as strong evidence for further preclinical and clinical investigation...