Drug Development and Industrial Pharmacy最新文献

Objective: The current research work focused on the evaluation of of H. rhamnoides and C. intybus Fe₂O₃ NPs against liver cancer cell line (HepG2) by performing antiproliferative assay targeting the RhoA gene and apoptotic pathway genes and proteins.

Methods: Fe₂O₃ NPs were synthesized using extracts of H. rhamnoides and C. intybus and characterized by UV-Vis spectroscopy, FTIR, SEM/EDS and XRD. MTT assay was used to study cytotoxicity against the HepG2 cells. Real-time qPCR and ELISA were used for the gene and protein analysis.

Results: An absorbance peak at 300 nm for H. rhamnoides and 289 nm for C. intybus nanoparticles were observed by UV-Vis analysis. The FTIR bands of H. rhamnoide Fe₂O₃ NPs suggested the presence of aldehydes, alcohols and polyols whereas bands of C. intybus Fe₂O₃ NPs suggested the presence of carboxyl groups, hydroxyl groups, alkynes and amines. The size of Fe₂O₃ NPs was found to be 27 ± 5nm for H. rhamnoides and 84 ± 4nm for C. intybus. The IC₅₀ value of 41.69 µM for H. rhmnoides and 71.04 µM for C. intybus Fe₂O₃ NPs compared to plant extract (78.10 and 96.03 µM for H. rhamnoides and C. intybus, respectively) were found against HepG2 cells. The gene expression and protein levels of RhoA were decreased whereas those of bax, caspase 3, caspase 8 and caspase 9 were found increased.

Conclusion: Nanoparticles and extract of H. rhamnoides were found more effective as compared to C. intybus, which was evident by the results of cytotoxicity and analysis of studied genes and proteins.

Objectives: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma.

Significance: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time.

Methods: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization.

Results: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic.

Conclusions: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Background: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.

Methods: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).

Results: Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC₅₀ = 1.4 μM) more than MCF-7/ADR cells (IC₅₀ = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC₅₀ = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC₅₀ = 7.2 μM) and SN (IC₅₀ = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC₅₀ from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC₂₀) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.

Conclusions: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

Objective: Carfilzomib (CFZ), a selective proteasome inhibitor, was encapsulated in pH-responsive niosomes to enhance its stability and targeted delivery.

Significance: This formulation aims to improve the controlled release and therapeutic efficacy of CFZ while minimizing systemic toxicity.

Methods: Niosomes were prepared via thin-film hydration using ergosterol, CHEMS, Span 60, and Tween 60. The lipid film was hydrated with PBS (pH 7.4) containing CFZ in DMSO at 60 °C, followed by sonication to form unilamellar vesicles. The formulation was characterized for encapsulation efficiency, particle size, drug release, cytotoxicity, and in vivo toxicity.

Results: Encapsulation efficiency reached 89.82%, with particle size increasing slightly from 323 nm (empty niosomes) to 334 nm (CFZ-loaded). In vitro release was pH-dependent, with 74.39% of CFZ released at pH 5.4 versus 54.55% at pH 7.4. CFZ-loaded niosomes exhibited enhanced cytotoxicity against breast cancer cells (IC₅。 = 0.0415 µM) compared to free CFZ (IC₅。 = 0.0714 µM). A synergistic effect with doxorubicin was observed (combination index <1). In vivo studies showed no significant toxicity at 1 and 2 mg/kg doses. However, 4 mg/kg caused elevations in liver enzymes, BUN, and creatinine, with histopathological signs of liver and kidney damage.

Conclusions: The CFZ-loaded niosomal system demonstrated optimal size, pH-responsive release, and superior anticancer activity. These findings highlight its potential as an effective carrier for controlled proteasome inhibitor delivery.

Introduction: Cancers are regarded as hazardous due to their high worldwide death rate, with breast cancer (BC), which affects practically all cancer patients globally, playing a significant role in this statistic. The therapeutic approach for BC has not advanced using standard techniques, such as specialized naringin (NG) chemotherapy. Instead, a novel strategy has been utilized to enhance smart drug delivery (SDD) to tumors.

Significance: Herein, we established NG-loaded zinc metal-organic framework-5 (NG-MOF-5) coated with liponiosomes (LNs) to manufacture NG-MOF-5@LNs nanoparticles (NPs) for antibacterial and cancer treatment.

Methods: MOF-5, NG, and NG-MOF-5@LNs were evaluated with XRD, thermogravimetric analysis (TGA), FTIR, SEM, TEM, PDI, ZP, encapsulation efficiency (EE), loading efficiency (LE), and drug release (DR) kinetics. We examined the antibacterial activity involving minimum inhibitory concentration (MIC) and zone of inhibition by NG, MOF-5, and NG-MOF-5@LNs. The cell viability, necrosis, and total apoptosis (late and early) were evaluated for anti-cancer activity against MCF-7 BC cells.

Results: TEM results demonstrated that NG-MOF-5@LNs formed monodispersed spherical-like particles with a size of 122.5 nm, PDI of 0.139, and ZP of +21 mV. The anti-microbial activity results indicated that NG-MOF-5@LNs exhibited potent antibacterial effects, as evidenced by inhibition zones and MIC values. The Higuchi model indicates an excellent fit (R² = 0.9988). The MTT assay revealed anti-tumor activity against MCF-7 BC cells, with IC₅₀ of 21 µg/mL for NG-MOF-5@LNs and demonstrating a total apoptosis effect of 68.2% on MCF-7 cells.

Conclusion: NG-MOF-5@LNs is anticipated to show as an effective antimicrobial and novel long-term-release antitumor agent and might be more suitable for MCF-7 cell therapy.

Objective: Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer.

Methods: The transferosomal formulation was optimized by employing a QbD approach with the design of experiment. A combination of screening and optimization design was used for formulation optimization. The optimized formulation was characterized by particle size, PDI, zeta potential, FTIR, XRD, and surface morphology using TEM. In vitro and ex vivo studies were performed using Franz diffusion cells. An in vitro cell line study was performed on the human melanoma A375 cell line.

Results: The optimized formulation has a particle size of 192.37 ± 13.19 nm, PDI of 0.41 ± 0.03, zeta potential -47.80 ± 3.66, and an entrapment efficiency of 64.11 ± 3.75%. In vitro release studies showed that ITZ encapsulated transferosomes offer higher and sustained release than pure drugs. Ex vivo drug penetration and retention studies show that the penetration and retention of transferosomes are more visible in the skin than in the drug. The cell viability study confirms that ITZ encapsulated transferosomes have almost 2-fold more potency against the A375 cell line than pure drug.

Conclusion: ITZ encapsulated transferosomes were successfully prepared and optimized using a combination of screening and optimization designs. Based on ex vivo and cell line studies, we conclude that ITZ-loaded transferosomes could aid melanoma management alongside standard therapies.

Objective: Orodispersible films (ODFs) are a convenient form of pediatric drug delivery and for those with swallowing difficulties. They can be extemporaneously prepared in pharmacies using pre-formulated bases which simplify and fasten the process while reducing compounding errors. OrPhylloTM is a water-based commercial vehicle for preparing polymeric ODFs. It is chemically compatible with various clinically relevant active pharmaceutical ingredients (APIs) at different drug loadings.

Methods: This study focuses on characterizing placebo OrPhylloTM films, including their morphological, mechanical, and textural properties, as well as physicochemical stability by thermal analysis and X-ray diffraction.

Results: After local ethical approval, healthy adults explored stickiness, mouthfeel, and disintegration of these 3 × 3 cm ODFs following various modes of administration. OrPhyllo™ ODFs (185 ± 10 µm thick) exhibited distinct surface characteristics, one side (lower) smoother and the upper side rougher, as observed and shown by scanning electron and atomic force microscopy. However, both sides demonstrated similar mucoadhesive properties and rapid disintegration (between 60 and 140 s, depending on the method used). Both sides were well-accepted, whether administered on the tongue or in the cheeks, with minor differences in mouthfeel and fast disintegration perception. The hen's egg chorioallantoic membrane test showed no irritancy, supporting the good acceptability of these placebo ODFs. The films remained structurally stable over 6 months, with low residual moisture.

Conclusion: The comprehensive in vitro and in vivo characterisation confirmed the suitability of OrPhylloTM ODFs for pharmaceutical applications.

Objective: Febuxostat (FBX) has been crystallized using bentonite dispersion as an antisolvent, and characterized by heat of fusion and heat of transition rule for possible polymorphic transformation and improved dissolution.

Significance: Polymorphic transformation may exhibit significant alteration of melting temperature, solubility, dissolution rate, and stability. FBX is known for polymorphic/hydrate/solvate transformation in many forms wherein stable form has hardly been reported.

Methods: Aqueous bentonite dispersion was used as antisolvent for crystallization of FBX and characterized by heat of fusion and heat of transition rule, and the effect of bentonite concentration on in vitro drug dissolution has also been confirmed.

Results: Monotropic and enantiotropic relationships between the pair of polymorphs have been established with the help of transition enthalpy and transition entropy rule. Energy-entropy interplay showed that the transition occurred above the melting temperature indicating the monotropic relation between the FBX crystal pairs (from A to Q). Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies also confirmed the transformation of A (pure FBX) to Q form and its stability (40 °C, 75%RH, 3 months). The crystallite size was estimated from the graphical plot of major important XRD peaks using the least square method of altered Scherrer equation which is supposed to minimize the error associated with the original Scherrer equation. Williamson-Hall equation was used properly for determining strain from the positive slope avoiding misperception of negative slope.

Conclusions: Prepared form Q was found stable and displayed in-vitro drug dissolution in an improved and controlled manner.

Objective: The purpose of this review is to elaborate current development and challenges of oral albumin nanoparticles, and realize their clinical application.

Significance: Albumin is an emerging protein nanocarrier with a high degree of versatility, safety, stability, modifiability. These characteristics endow albumin nanoparticles with considerable attention and unique roles in drug delivery. However, most albumin nanoparticles are administered intravenously instead of orally, although oral administration is the most popular and common drug delivery route. Oral administration of albumin nanoparticles is their inevitable tendency, but researches referred to this area are still in infancy.

Methods and results: Given that, firstly, the basic properties of albumin nanoparticles, like preparation methods, drug loading strategies, targeted drug delivery, and clinical application were simply discussed to provide design guide for their oral administration. Subsequently, the functions and challenges of albumin nanoparticles in oral drug delivery, and strategies to overcome the barriers were highlighted. Finally, aiming to realize their clinical potentials, the possible future trends of orally administrated albumin nanoparticles were also elaborated.

Conclusions: In this review, albumin nanoparticles were comprehensively introduced, especially their functions and challenges in oral drug delivery, aiming to guide their design and development.

Objective: This review explores green approaches to enhance poorly water-soluble drug solubility. Implementing sustainable and green techniques, it provides a comprehensive overview of advancements and applications in drug development.

Significance of review: Drug solubility is a key challenge in pharmaceutical research, affecting bioavailability and efficacy. Conventional methods often rely on hazardous solvents and energy-intensive processes, posing environmental and safety concerns. This review emphasizes green chemistry principles as sustainable alternatives to enhance solubility while supporting global sustainability goals.

Key findings: Natural and biodegradable polymers in solid dispersions offer effective, eco-friendly solubility enhancement. The application of supercritical CO₂ demonstrates significant potential as a green solvent for solubility enhancement, offering scalability while minimizing environmental impact. Plant-derived and renewable excipients offer a sustainable alternative to synthetic additives.

Summary of challenges: Natural polymers face formulation, solubility, and batch variability issues. Deep eutectic solvents and ionic liquids face stability, regulatory hurdles, toxicity risks, and hygroscopicity. Supercritical fluid technology requires costly equipment and precise optimization. Green co-crystallization faces co-former selection, scalability, and stability issues. Further refinement, safety validation, and industrial feasibility studies are needed.

Potential drawbacks of green approaches: Green solubility enhancement methods face scalability, regulatory, and cost challenges. Some offer limited solubility gains and stability issues. Ensuring cost-effectiveness, industrial viability, and compliance is key for broader adoption.

Conclusion: Green solubility enhancement offers a sustainable solution to drug solubility challenges. Integrating these methods improves efficiency, safety, and environmental impact. This review highlights the need for further research and the adoption of sustainable drug delivery approaches.