Therapeutic delivery最新文献

Aim: Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery.

Method: A 3³ Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties. Furthermore, the optimized lipid nanocapsule was loaded into a hydrogel and evaluated for rheology, spreadability, ex-vivo skin permeation, deposition and irritation.

Results: The numerical optimization suggested an optimal formula with desirability value of 0.852 and low prediction errors. The optimized formulation showed good % drug entrapment efficiency (79.56 ± 2.34%), nanometer size (56.68 ± 1.2 nm), monodisperse nature (PDI = 0.176 ± 0.2), spherical morphology and good drug-excipient compatibility. The raloxifene hydrochloride loaded lipid nanocapsule hydrogel showed shear thinning properties, sustained drug delivery, dermal compatibility and significantly higher permeability (2-fold), retention (3.37) for raloxifene hydrochloride compared to the control.

Conclusion: The present study showed a successful development of raloxifene hydrochloride loaded lipid nanocapsule hydrogel with improved skin permeation, retention, and good topical compatibility. This formulation may overcome the challenges associated with raloxifene hydrochloride oral delivery including low bioavailability.

Aim: Voriconazole (VRZ) is highly effective in treating invasive pulmonary aspergillosis (IPA), in addition to hepatotoxicity. Therefore, the current study focuses on the development and characterization of voriconazole-loaded microspheres (VRZ@PCL MSPs) to augment pulmonary localization and antifungal efficacy.

Methods: VRZ@PCL MSPs were fabricated by using the o/w emulsion method. The optimized F3VRZ@PCL MSPs were subjected to physicochemical characterization, in vitro release, hemocompatibility, antifungal efficacy as well as pharmacokinetic and biodistribution evaluation.

Results: The optimized F3VRZ@MSPs exhibited a particle size (10.90 ± 2.61 µm), entrapment efficiency (19.35 ± 2.47%), drug loading (3.22 ± 0.41%) with sustained release behavior up to 24 h and hemocompatibility upto 50 µg/mL. Results of antifungal testing indicated the superior antifungal potential of F3VRZ@PCL MSPs as compared to free VRZ and nystatin. In vivo pharmacokinetic evaluation in Sprague-Dawley rats displayed 12.5-fold and 4.5-fold increments, respectively, in t_1/2 and AUC_0-t of F3VRZ@PCL MSPs as compared to free VRZ. Moreover, F3VRZ@PCL MSPs displayed relatively higher lung targeting with a drug targeting index (DTI) of 0.213 as compared to DTI of 0.037 of free VRZ.

Conclusion: In conclusion, F3VRZ@PCL MSPs offer a promising approach for sustained and targeted delivery of VRZ and hold the potential to offer high therapeutic efficacy in the treatment of IPA.

Aim: The goal of the present work was to formulate zein-decorated rifaximin (RFX) nanosuspension to attain sustained release as well as effectiveness against Escherichia coli (E. coli).Methods: The RFX nanosuspension was fabricated by using antisolvent addition method followed by coating using hydroalcoholic zein solution. The optimized RFX-NS and RFX-NS@zein was lyophilized for further spectroscopic evaluations. In vitro antibacterial potential was elucidated using well diffusion method whereas MIC value was determined by microbroth dilution method against E. coli for RFX-NS and pure RFX.Results: Box-Behnken Design was employed to assess the effects of independent variables on quality target product profile of RFX-NS. Optimized RFX-NS depicted particle size of 193.5 ± 4.45 nm with 76.49 ± 1.71% drug content. The significant change in particle size and zeta potential confirmed the formation of zein coated RFX-NS (RFX-NS@zein). In vitro release study depicted, 96.91 ± 1.21% release of RFX from RFX-NS in 6 h whereas 97.47 ± 1.99% RFX release was observed from RFX-NS@zein at the end of 12 h. Antibacterial assay of RFX-NS and free RFX against E. coli displayed MIC value of 15.44 ± 0.01 μg/ml and 72.96 ± 0.25 μg/ml, respectively.Conclusion: The results highlighted a significance of nanosuspension for improving the solubility of RFX and its antibacterial potential against E. coli.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

Aims: To enhance the therapeutic potential of Cabozantinib (CBZ), a tyrosine kinase inhibitor with limited water solubility, low bioavailability, and high toxicity, by developing a Cabozantinib-Phospholipid Complex (CBZ-PLS).

Materials & methods: CBZ-PLS was formulated using solvent evaporation with a Box-Behnken design and characterized using various techniques to confirm molecular interactions. Solubility, in vitro release, pharmacokinetics, and toxicity were evaluated. Cytotoxic effects on HepG2 cell lines were also assessed.

Results: CBZ-PLS exhibited a 126-fold increase in solubility and enhanced CBZ release in vitro. Pharmacokinetic studies on Wistar rats demonstrated a 1.58-fold increase in bioavailability, while acute toxicity studies confirmed biocompatibility. CBZ-PLS showed superior cytotoxicity, apoptosis induction, migration inhibition, increased ROS generation, and greater DNA fragmentation in HepG2 cells. The complex also maintained stability over 6 months.

Conclusions: CBZ-PLS significantly improves the solubility, bioavailability, and therapeutic efficacy of CBZ against liver cancer, presenting a promising approach for more effective liver cancer treatment.

Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors, with a high prevalence in elderly population. Most chemotherapeutic agents fail to reach the tumor site due to various challenges. However, smart nanocarriers have demonstrated excellent drug-loading capabilities, enabling them to cross the blood brain tumor barrier for the GBM treatment. Surface modification of nanocarriers has significantly enhanced their potential for targeting therapeutics. Moreover, recent innovations in drug therapies, such as the incorporation of theranostic agents in nanocarriers and antibody-drug conjugates, have offered newer insights for both diagnosis and treatment. This review focuses on recent advances in new therapeutic interventions for GBM, with an emphasis on the nanotheranostics systems to maximize therapeutic and diagnostic outcomes.

Aims: Breast cancer is the second leading cause of death worldwide. Conventional chemotherapeutic therapies lack the specific targeting effect toward the cancerous cells resulting in extensive side effects. Our current study endeavors to prepare novel bioinspired folic acid-functionalized caffeic acid (CA)-loaded casein nanoparticles (CS NPs) for curbing breast cancer.

Methods: CA-CS NPs were prepared by simple coacervation method followed by lyophilization. Functionalized CS NPs were achieved using folic acid as the targeting moiety. Entire comparative characterization between unconjugated and conjugated NPs were implemented in terms of size, polydispersity index, surface charge, ¹H-NMR, surface morphology, in-vitro drug release, sterilization, cytotoxicity, and animal studies.

Results: Conjugated NPs attained PS = 157.23 ± 2.64 nm, PDI = 0.309 ± 0.199, ZP = -25.53 ± 2.31 mV and IC50 = 40 ± 2.9 µg/ml. Significant reduction in the biochemical marker levels of Carcino-embryonic antigen, carbohydrate antigen 15-3, and malondialdehyde while increased superoxide dismutase levels were achieved in the tumor -induced rats treated by the conjugated NPs. Histopathological examinations showed great improvement in the mammary and necrotic regions.

Conclusion: The present work paves the road of 'back to nature' approach in designing biocompatible bioinspired conjugated nanocarriers for the diagnosis and treatment of various diseases.