Therapeutic delivery最新文献

In the twenty-first century, cancer continues to be a significant worldwide health concern that requires immediate and ongoing attention. Currently, chemotherapeutic treatments are constrained by various limitations, including drug resistance, nonspecific distribution, and organ toxicity. These difficulties highlight the need for safer and more efficient substitutes, like Piperine (PPN), a bioactive alkaloid obtained from Piper longum and Piper nigrum, as a viable option for cancer therapy. The diverse pharmacological characteristics of PPN, such as anti-inflammatory, antioxidant, and anticancer, make it an intriguing natural substance. However, the poor aqueous solubility, low penetration, and poor pharmacokinetic behaviors of PPNs impede its clinical translation. The design of nanoformulations of PPNs can be a promising approach to overcome its limitations, improving therapeutic effectiveness and bioavailability, while facilitating targeted delivery and synergistic effect toward cancer therapy. The current review provides an in-depth overview of the latest developments in PPN-based nanoformulations, highlighting their potential to address persistent problems in cancer treatment and pave the way for their integration into clinical oncology.

Background: Considering unmet clinical needs in the dementia therapeutics world, PCMCV002 was developed as a cheap and easily accessible adjunct therapy option. It is a combination of amino acids, vitamins, and essential nutrients formulated in a best-fit complex medicinal food supplement as an adjunct therapy to the already established dementia therapies.

Aim: The aim of this study is to evaluate the sub-acute preclinical toxicity profile of PCMCV002 in Wistar rats.

Materials/method: PMCV002, ketamine, Photoelectric colorimeter model AE 11D (Erma Inc. Japan), Hematology analyzer (Sysmex USA), hematocrit, centrifuge, spectrophotometer, weighing balance, cotton wool, scissors, animal cages, plastic containers, plain and heparinized plastic bottles. The study involved hematology, hepatorenal and electrolytes changes and histological evaluation 28 days postdosing daily with PCMCV002 using OECD test Guideline 407 (2008).

Conclusions: The findings following a 28-day administration of PMCV002 revealed that it is relatively nontoxic in rats, as no obvious harmful effects were noted on hematological and biochemical indices. The histo-architecture of the brain, heart, liver, and kidneys following a 28-day administration of PCMCV002 to the test rats did not show any significant pathologic changes. All these indicate a quite safe medicinal product, coupled with maximum tolerable dose as high as 5000 mg/kg.

Aim: Glaucoma is associated with abnormal IOP elevation leading to irreversible blindness. In this study, we explore the therapeutic potential of thymoquinone in combination with travoprost to enhance the treatment efficacy of glaucoma.

Method: Thymoquinone-travoprost co-loaded liposomes (LP-TP-TQ) were formulated using thin-film hydration technique and optimized using BBD. Optimized liposomes underwent comprehensive ex vivo, in vitro, and preclinical characterization.

Results: The optimized formulation demonstrated a vesicle size of 96.02 ± 1.35 nm having negative surface charge encapsulated 81.55 ± 1.12% of TQ and 86.88 ± 0.55% of TP. LP-TP-TQ released drug sustained for 24 hr, while ex vivo permeation studies confirmed enhanced ocular penetration. In human corneal epithelial cells, LP-TP-TQ exhibited superior viability and internalization properties. The IOP-lowering efficacy was evaluated in an in vivo glaucomatous rabbit model, where significant reductions in IOP were observed, underscoring the potential of co-delivering TQ and TP via liposomes to ameliorate glaucomatous damage. Results suggest that LP-TP-TQ presents a promising strategy for advancing glaucoma management, laying the groundwork for future clinical investigations.

Aim: The imperative challenges in transdermal iontophoresis (IP) are irritation, skin polarization, and patient discomfort. In this paper, we studied the IP delivery of oxycodone (OXC) using continuous direct current (CDC) and pulse depolarization current (PDC) current protocols.

Methods: The different current protocols (CDC, PDC1, PDC2, and PDC3) have been employed to investigate the in vitro transdermal IP of OXC through the rat skin. Moreover, other effective factors including the formulation pH, the magnitude of applied current density, and the NaCl concentration were optimized to obtain the best performance of IP.

Results: The in vitro permeation experiments demonstrated that the cumulative amount of permeated OXC after 24 h (Q_24 h) in the presence of the studied current protocols decreases in the following order: CDC > PDC3 > PDC2 ≈ PDC1. The permeation of OXC in the presence of CDC was evidently enhanced compared to that of the PDC3. Also, the experimental data were fitted using the Peppas-Sahlin model. Finally, in vivo experiments revealed that a statistically significant increase in the permeated OXC in the presence of IP technique (CDC, and PDC3) as compared to the control experiment.

Conclusion: The study can pave the way for developing IP delivery systems using PDC.

Aims: Luliconazole is a class of imidazole that exhibits high antifungal activity. Luliconazole has drawbacks, such as low aqueous solubility and poor skin penetration.

Methods: To overcome these limitations, luliconazole-loaded bilosomes (LZBSs) were developed via ethanol injection, using soy lecithin, cholesterol, Span 60, and bile salt. A 2³ factorial design was employed to optimize the formulation.

Results: The optimized batch of LZBS resulted in a vesicle size of 177.3 ± 0.00 nm with an entrapment efficacy of 90.0 ± 2.5 % and zeta potential of -54.8 ± 3.15 mV. TEM analysis confirmed the spherical shape of bilosome vesicles and ATR-FTIR results supported the formation of bilosomes without any interaction. LZBS was loaded into Carbopol gel (LZBS gel) and evaluated for in vitro and ex vivo drug release study; results showed extended release of 90.53 ± 7.89 % and 84.97 ± 5.58 %, respectively, up to 24 h. Antifungal study for LZBS gel demonstrated superior activity against Candida albicans as compared to marketed and pure drug.

Conclusion: Thus, luliconazole-loaded bilosome gel proved to be effective against fungal infections.

Aims: Curcumin (CUR) exhibits strong therapeutic potential for Alzheimer's disease due to its antioxidant, neuroprotective, anti-inflammatory, and anti-amyloid effects. However, its clinical application is limited by poor brain bioavailability. This study aimed to enhance CUR delivery to the brain via nasal administration using a novel formulation of polyethylene glycol (PEG)-functionalized carboxylated (COOH) Multi-Walled Carbon Nanotubes (MWCNT).

Materials and methods: CUR-loaded MWCNT-COOH-PEG was developed and optimized using a 3² factorial design. The system was characterized for entrapment efficiency, particle size, zeta potential, and in vitro release. Neuroprotective efficacy was assessed through apoptosis inhibition in PC12 cells, and CUR concentration in the brain was measured post-nasal administration.

Results: The formulation achieved an entrapment efficiency of 91.4 ± 0.8%, a zeta potential of -31.1 ± 1.05 mV, and a particle size of 310 ± 7.92 nm. In vitro release was 95.42 ± 0.0004% at pH 5.5 and 89.98 ± 0.0039% at pH 7.4. CUR at 18.75 µg/mL inhibited apoptosis in PC12 cells after 24 h. Higher brain CUR concentrations were observed 4 h post-administration.

Conclusion: CUR-loaded MWCNT-COOH-PEG effectively enhances brain bioavailability of CUR, demonstrating significant neuroprotective effects, and offers a promising approach for Alzheimer's therapy.

Aim: MXene pertains to the family of two-dimensional materials with excellent surface area, biocompatibility, and many possibilities for surface functionalization. Owing to this, a multifunctional MXene nanocomposite was developed for targeted drug delivery at tumor site as current treatment regimens show increased adverse effects and limited selectivity.

Method: MAX phase titanium aluminum carbide (Ti₃AlC₂) was synthesized, which serves as the precursor for the production of Ti₃C₂T_X MXene. Additionally, green-synthesized silver nanoparticles (AgNP) were affixed onto the MXene's surface, forming the MXene@AgNP nanocomposite. This nanocomposite was further employed as a drug delivery carrier to deliver chemotherapeutic drug, docetaxel (DTX), linked covalently to the MXene@AgNP via polyethylene glycol (PEG), resulting in the final composition of MXene@AgNP@PEG@DTX.

Result: The final nanocomposite exhibits both thermal and pH-responsive in vitro drug delivery capabilities, with maximum drug release of 60% at pH 5.4 after 48 hours. The IC₅₀ value for final nanocomposite was determined at 2.698 µg/mL, significantly lower than IC₅₀ value 9.630 µg/mL for DTX against breast carcinoma. Enhanced cellular uptake of the MXene@AgNP carrier was confirmed through cellular uptake studies.

Conclusion: This work broadens the scope for therapeutic approach toward cancer through the development of nanocomposite by providing a potent and biocompatible alternative.

Purpose: To develop and characterize a micellar system, SMA-TQ (styrene-maleic acid-thymoquinone), for the potential management of triple-negative breast cancer (TNBC).

Methods: SMA synthesis and TQ encapsulation in SMA are described. The loading of TQ in SMA-TQ was established at 20%. The size of SMA-TQ micelle as determined by DLS was in average of 155.2 nm with a polydispersity index of 0.350. In vitro testing was carried out in 4T1 TNBC cell line, and in vivo testing in mice model of TNBC.

Results: In vitro experiments revealed an added effect of SMA-TQ and doxorubicin (Doxo) at doses of 1-3 mM). In vivo studies showed that the combination of SMA-TQ and Doxo had the least mean tumor growth (509.6%) compared to other treatments.

Conclusion: Obtained results collectively suggest that the combination of SMA-TQ and Doxo has cumulative effects in inhibiting tumor growth, emphasizing the significance of combination therapies to enhance anticancer effectiveness. This work reveals SMA-TQ micellar system as complementary therapeutic option in TNBC.