Drug Delivery and Translational Research最新文献

Long-acting injectables have gained attraction as a system for treating chronic conditions due to their increased efficacy, safety, and patient compliance. Currently, patients with Parkinsons need to administer oral medications multiple times a day which imposes the significant risk of non-compliance. This study aimed to design an in-situ implant-forming system for controlled delivery of levodopa and carbidopa for up to 1 week which will reduce the need for multiple dosing. The combination of poly-lactic-co-glycolic acid (PLGA _50:50) and Eudragit L-100 was used to prepare the implants and the formulation was optimized to achieve a controlled release over 7 days. The optimized formulation containing 26% PLGA and 6% Eudragit L 100 displayed a favorable release profile and injectability with low viscosity. The optimized formulation in vitro release study revealed an initial burst of 34.17% and 37.16% for levodopa and carbidopa in the first 24 h and about 92% and 81% release within 7 days. A good correlation was observed between the in-vitro drug release data and ex-vivo drug release with a correlation coefficient of 0.91 for levodopa and 0.90 for carbidopa. Viscosity analysis showed the Newtonian behavior of the formulation. Syringeability analysis of the formulation showed that the maximum force required for expelling the formulation was 32.98 ± 0.72 N using a 22 G needle. The in-vitro degradation studies revealed 81.89% weight loss of implant in 7 days. The prepared formulation was assessed for in-vivo performance using a convolution modeling technique using a convolve function in R software. The predicted AUC 0-∞ h for the in-situ forming implant was 26505.5 ng/ml with Cmax, 399.3 ng/ml, and Tmax 24 h assuming 100% bioavailability. The results justify that the prepared in-situ implant forming system can be a promising system for the delivery of levodopa and carbidopa for Parkinson's patients.

Doxorubicin (DOX), an anthracycline, is widely used in cancer treatment by interfering RNA and DNA synthesis. Its broad antitumour spectrum makes it an effective therapy for a wide array of cancers. However, the prevailing drug-resistant cancer has proven to be a significant drawback to the success of the conventional chemotherapy regime and DOX has been identified as a major hurdle. Furthermore, the clinical application of DOX has been limited by rapid breakdown, increased toxicity, and decreased half-time life, highlighting an urgent need for more innovative delivery methods. Although advancements have been made, achieving a complete cure for cancer remains elusive. The development of nanoparticles offers a promising avenue for the precise delivery of DOX into the tumour microenvironment, aiming to increase the drug concentration at the target site while reducing side effects. Despite the good aspects of this technology, the classical nanoparticles struggle with issues such as premature drug leakage, low bioavailability, and insufficient penetration into tumours due to an inadequate enhanced permeability and retention (EPR) effect. Recent advancements have focused on creating stimuli-responsive nanoparticles and employing various chemosensitisers, including natural compounds and nucleic acids, fortifying the efficacy of DOX against resistant cancers. The efforts to refine nanoparticle targeting precision to improve DOX delivery are reviewed. This includes using receptor-mediated endocytosis systems to maximise the internalisation of drugs. The potential benefits and drawbacks of these novel techniques constitute significant areas of ongoing study, pointing to a promising path forward in addressing the challenges posed by drug-resistant cancers.

The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.

Vitamin D₃-loaded lipid nanoparticles (Vit D₃-LNP), integrated into an azulene cream, were developed to enhance the topical delivery and stability of Vitamin D₃. The LNP was formulated using a lipid mixture and hot homogenization-ultrasonication, with comprehensive characterization revealing a particle size of 153.9 nm, a high zeta potential (-54.3 mV), and a PDI of 0.216, which TEM confirmed. Encapsulation efficiency was high (96.98%), indicating successful incorporation of Vitamin D₃ within the lipid matrix. Stability studies revealed the impact of light exposure on Vitamin D₃ degradation. In vitro, release, and skin penetration studies using Franz diffusion cells and two-photon microscopy demonstrated enhanced drug permeation and retention in deeper skin layers with the cream formulation. Cell Viability test confirmed high cell viability (~ 80-100%) for both free Vitamin D₃ and the LNP formulation; also inflammation test showed a significant reduction in ROS levels with Vitamin D₃-LNP treatment. These findings highlight the therapeutic value of LNP in managing conditions like Vitiligo, providing insights into the design of stable, effective Vitamin D₃ delivery systems for dermal applications, and offering a promising approach for advanced skin treatments.

This study aims to create glyco-based nanoparticles (NPs) with high drug-loading capability for targeted cancer treatment, specifically against MDA-MB-231 breast cancer cells. Traditional NPs have faced limitations due to low drug-loading capacities, leading to suboptimal therapeutic effectiveness and significant side effects. To overcome these limitations, DOX@pB-pM NP were synthesized using a self-assembly combination method of two poly(ε-caprolactone) (PCL) based polymers, mannoside-b-PCL (pM) and phenylboronic acid (PBA)-mPEG-t-PCL (pB). The pM polymer synthesis includes a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc) reaction. DOX@pB-pM NP's mannose moiety is specifically engineered to target MDA-MB-231 cells, while the core of the NPs is made of hydrophobic, biodegradable polyester PCL. The functions of mPEG and PBA in the pB tri-block copolymer are to enhance biocompatibility and drug-loading efficiency, respectively. Additionally, mPEG can reduce nonspecific interactions. The PBA on the pB introduces a hydrophobic segment to the copolymer, which can improve the interaction with water-insoluble drugs, doxorubicin (DOX). The PBA moiety can also provide additional functionality, such as pH-responsive and H₂O₂-responsive drug release, which is particularly useful in targeting the tumor's acidic and oxidative microenvironment. The PBA groups convert them to boronic acid and 4-(hydroxymethyl) phenol, which destroys the NP core and causes DOX release, resulting in cell death. The in vitro release profile of DOX from the DOX@pB-pM NPs was evaluated under various conditions, including different pH levels and the presence or absence of H₂O₂, to simulate the acidic tumor microenvironment. The cytotoxicity of the DOX@pB-pM NPs was assessed using the MTT assay, which demonstrated significant inhibition of MDA-MB-231 breast cancer cell growth by DOX@pB-pM NPs. By combining mannose for the targeting of MDA-MB-231 breast cancer cells and fine-tuning the ratio of pM and pB polymers, the NPs showed good therapeutic efficacy. Importantly, pB-pM NPs displayed good biocompatibility, with no significant effect on cell survival even at high concentrations, indicating their potential as safe drug carriers. These data show that DOX@pB-pM NPs can potentially improve cancer therapeutic efficacy and safety.

Plant oils play an important role in natural product-based dermatological formulations owing to their multifunctional therapeutic properties. Among these, sunflower seed oil (SSO) has gained prominence due to its dual role as a barrier-restoring emollient and skin penetration enhancer. Rich in unsaturated fatty acids, particularly linoleic acid (LA) and oleic acid (OA), SSO supports skin health by restoring lipid bilayer organization, modulating ceramide synthesis, and activating peroxisome proliferator-activated receptor-alpha (PPAR-α). These mechanisms reinforce barrier integrity while facilitating transdermal delivery of active agents. However, oils high in OA and/or containing protein allergens may compromise barrier function and promote allergen penetration, necessitating careful evaluation of chemical composition and structural characteristics. Ex vivo studies using porcine skin models have demonstrated SSO ability to enhance the permeation of both hydrophilic and lipophilic compounds. Clinically, SSO has shown efficacy in reducing transepidermal water loss (TEWL), improving hydration, and accelerating wound healing in conditions such as xerosis and atopic dermatitis. Its favourable safety profile, biocompatibility, and successful incorporation into various dermatological and cosmeceutical formulations underscore its versatility. This review critically examines the molecular interactions between SSO and the skin barrier, with specific focus on its roles in barrier restoration, inflammation modulation and transdermal enhancement. Mechanistic insights from its fatty acid composition are integrated with ex vivo findings, supported by clinical evidence, to evaluate its therapeutic potential and utility as a multifunctional, plant-based excipient in modern topical drug delivery systems for human skin health.

The accelerating rate of antibiotic resistance has always been one of the leading causes of increased skin and soft tissue infections (SSTIs) burden around the globe. Current treatments mainly focus on systemic antibiotics indicated for both uncomplicated and complicated SSTIs that act as a contributing factor secondary to widespread systemic exposure. Topical formulation of antibacterial agents or antibiotics are renowned for their targeted and localised action in the skin which appears as an intriguing clue to the resistance problem. Nevertheless, there are several deterrents associated with conventional topical formulations including drug permeability and skin retention. This has propelled the transformation of SSTI intervention towards the incorporation of nanotechnology to enhance topical drug delivery for SSTIs. This review outlines the advancement of nanoparticle-based topical formulations against SSTIs, covering cellulitis and erysipelas, boils and carbuncles, impetigo, cutaneous non-tuberculous mycobacterial infections and leprosy, as well as pitted keratolysis. Pre-clinical safety profile and antibacterial efficacy of topical nanoformulations were comprehensively reviewed and classified into multiple categories such as metal nanoparticles, emulsion-based nanosystems, nanovesicles, lipid nanoparticles and polymeric nanoparticles. The up-to-date patent trends on topical nanoformulations for SSTIs up to 2025 were also analysed and justified based on current evidence to pinpoint the research gap and future prospects in this growing area of research. It is anticipated that topical nanoformulations can potentially stand in for conventional topical formulations to treat SSTIs attributed to their pronounced antibacterial activity and tolerability.

Lipid-polymer hybrid nanoparticles (LPN) are an integration or "collaboration" between the two distinct drug delivery platforms of lipid and polymeric carriers. The idea centres on coining the advantages of both materials while attempting to overcome the limitations inherent to each component, thus improving biocompatibility, drug loading, stability, size uniformity, and controlled release properties. Since their emergence over two decades ago, LPN have attracted growing interest in various therapeutic areas such as cancer, neurological disorders, osteoarthritis, and COVID-19 viral infections. Their structural diversity has expanded from the classical polymeric core-lipid shell to its inverse structure of lipid core-polymeric shell and homogeneous lipid-polymer blends, producing nine types of LPN under these structural classes. Correspondingly, preparation strategies have evolved from two-step methods to integrated one-step method of nanoprecipitation, single-emulsification-solvent evaporation, and double-emulsification-solvent evaporation in the early 2010s. More recently, novel methods such as self-assembly, modified ionic gelation, modified ethanolic injection, film rehydration, and hot-melt emulsification have been introduced, with hot-melt emulsification showing particular promise for scalability. In this context, the present review proactively introduces an updated structural classification and proposes a revision of existing formulation strategies by expanding the one-step and two-step framework to incorporate emerging methods tailored for dermatological applications. While LPN are often portrayed as a better version of lipid and polymeric-based nanoparticles, their practical applicability in dermatological treatments remains an open question. Therefore, this review evaluates LPN's clinical and translational potential in dermatology applications such as, wounds, skin infections, dermatitis, psoriasis, skin cancer, pain management, and cosmetic applications.

The pulmonary route has gained significant attention as a drug delivery method, particularly for managing respiratory diseases. This approach provides several benefits, such as rapid therapeutic action, minimized systemic exposure, improved patient adherence, and the ability to deliver high drug concentrations directly to the lungs. Advances in inhalation devices, including pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulizers, have established the pulmonary route as effective for administering both small-molecule drugs and complex biologics. Recent research has showcased the successful use of inhaled biologics such as monoclonal antibodies, nanobodies, and protein-based treatments in conditions like asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, COVID-19, and respiratory syncytial virus (RSV). These treatments employ innovative mechanisms, such as muco-trapping and immune modulation, to optimize site-specific drug delivery and minimize systemic side effects. As technologies for pulmonary administration continue to evolve, they provide a non-invasive and highly promising platform for enhancing respiratory therapies and broadening the applications of biologics.

The advent of RNA interference (RNAi) technology through the use of short-interfering RNAs (siRNAs) represents a paradigm shift in the fight against viral infections. siRNAs, with their ability to directly target and silence specific posttranscriptional genes, offer a novel mechanism of action distinct from that of traditional pharmacotherapeutics. This review delves into the growing field of siRNA therapeutics against viral infections, highlighting their critical role in contemporary antiviral strategies. Importantly, this review will solely focus on the use of lipid nanoparticles (LNPs) as the ideal antiviral siRNA delivery agent for use in vivo. We discuss the challenges of siRNA delivery and how LNPs have emerged as a pivotal solution to enhance antiviral efficacy. Specifically, this review focuses on work that have preclinically tested LNP formulated siRNA on virus infection animal models. Since the COVID-19 pandemic, we have witnessed a resurgence in the field of RNA-based therapies, including siRNAs against viruses including, SARS-CoV-2. Notably, the critical importance of LNPs as the ideal carrier for precious 'RNA cargo' can no longer be ignored with the advent of mRNA-LNP based COVID-19 vaccines. siRNA-based therapeutics represents an emerging class of anti-infective drugs with a foreseeable future as suitable antiviral agents.