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1.
Int J Nanomedicine ; 19: 5021-5044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832335

RESUMO

Nanoparticle systems integrating alginate and chitosan emerge as a promising avenue to tackle challenges in leveraging the potency of pharmacological active agents. Owing to their intrinsic properties as polysaccharides, alginate and chitosan, exhibit remarkable biocompatibility, rendering them conducive to bodily integration. By downsizing drug particles to the nano-scale, the system enhances drug solubility in aqueous environments by augmenting surface area. Additionally, the system orchestrates extended drug release kinetics, aligning well with the exigencies of chronic drug release requisite for antibacterial therapeutics. A thorough scrutiny of existing literature underscores a wealth of evidence supporting the utilization of the alginate-chitosan nanoparticle system for antibacterial agent delivery. Literature reviews present abundant evidence of the utilization of nanoparticle systems based on a combination of alginate and chitosan for antibacterial agent delivery. Various experiments demonstrate enhanced antibacterial efficacy, including an increase in the inhibitory zone diameter, improvement in the minimum inhibitory concentration, and an enhancement in the bacterial reduction rate. This enhancement in efficacy occurs due to mechanisms involving increased solubility resulting from particle size reduction, prolonged release effects, and enhanced selectivity towards bacterial cell walls, stemming from ionic interactions between positively charged particles and teichoic acid on bacterial cell walls. However, clinical studies remain limited, and there are currently no marketed antibacterial drugs utilizing this system. Hence, expediting clinical efficacy validation is crucial to maximize its benefits promptly.


Assuntos
Alginatos , Antibacterianos , Quitosana , Nanopartículas , Quitosana/química , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Humanos , Nanopartículas/química , Tamanho da Partícula , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Testes de Sensibilidade Microbiana , Animais , Sistemas de Liberação de Medicamentos/métodos , Solubilidade , Bactérias/efeitos dos fármacos
2.
Front Pharmacol ; 15: 1353503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434698

RESUMO

Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).

3.
Tissue Eng Regen Med ; 20(7): 1053-1062, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37682505

RESUMO

BACKGROUND: Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis on the effectiveness of secretome in promoting wound healing. METHODS: To ensure the rigor and transparency of our study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, as registered in PROSPERO with ID: CRD42023412671. We conducted a comprehensive search on four electronic databases to identify studies evaluating the effect of secretome on various clinical parameters of wound repair. In addition, we evaluated the risk of bias for each study using the Jadad and Newcastle-Ottawa scale. To synthesize the data, we employed a fixed-effects model and calculated the mean difference or odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Based on six included articles, secretome is known to affect several clinical parameters in wound healing included the size and depth of ulcers during healing; the E´chelle d'évaluation clinique des cicatrices d'acne (ECCA) score, epidermal thickness, collagen fibers, abnormal elastic tissues, volume of atrophic acne scars, skin pore volume, and erythema during acne scar healing; and microcrust areas, erythema index, transepidermal water loss, volume of atrophic acne scars, erythema, and relative gene expression of procollagen type I, procollagen type III, and elastin were evaluated in wound healing after laser treatment. Meta-analysis studies showed that secretome reduced ulcer size (mean difference: 0.87, 95% CI of 0.37-1.38, p = 0.0007), decreased ulcer depth (mean difference: 0.18, 95% CI of 0.11-0.25, p < 0.00001), and provided patient satisfaction (odds ratio: 9.71, 95% CI of 3.47-21.17, p < 0.0001). However, secretome failed to reach significance in clinical improvement (OR 0.38, 95% CI 0.10, 1.53, p = 0.06). CONCLUSION: The secretome provides good effectiveness in accelerating wound healing through a mechanism that correlates with several clinical parameters of wound repair.


Assuntos
Acne Vulgar , Cicatriz , Humanos , Cicatriz/patologia , Cicatriz/terapia , Eritema , Secretoma , Úlcera
4.
Polymers (Basel) ; 15(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37765512

RESUMO

α-mangostin (Amg), a compound isolated from the mangosteen rind (Garcinia mangostana, L.), has demonstrated promising anticancer activity. However, its low solubility and selectivity against cancer cells limit its efficacy. To address this issue, researchers have developed chitosan/alginate polymeric nanoparticles (NANO-AMCAL) to enhance the effectiveness of Amg. In vitro studies have demonstrated that NANO-AMCAL is highly active against breast cancer cells. Therefore, an in vivo study was conducted to evaluate the efficacy of NANO-AMCAL in treating breast cancer in Wistar rats (Rattus norvegicus) and determine the effective dose. The rats were divided into seven treatment groups, including positive control, negative control, pure Amg, and NANO-AMCAL 5 mg, 10 mg, and 20 mg. The rats were injected subcutaneously with a carcinogenic agent, 7,12-dimethylbenz(a)anthracene (DMBA) and were evaluated for weight and tumor volume every three days during treatment. Surgery was performed on day 14, and histopathological studies were carried out on breast and lung cancer tissues. The results showed that NANO-AMCAL significantly enhanced the anticancer activity of Amg in treating breast cancer in Wistar rats. NANO-AMCAL containing 0.33 mg of Amg had a healing effect three times better than 20 mg pure Amg and was comparable to tamoxifen. The effective dose of NANO-AMCAL for anti-breast cancer treatment in Wistar rats was found to be 20 mg, which exhibited a good healing response, and the tumor volume continued to decrease up to 17.43% on the 14th day. Furthermore, histopathological tests showed tissue repair and no metastases. These findings suggest that NANO-AMCAL may be a promising therapeutic option for breast cancer treatment.

5.
Molecules ; 27(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557827

RESUMO

Most recently discovered active pharmaceutical molecules and market-approved medicines are poorly soluble in water, resulting in limited drug bioavailability and therapeutic effectiveness. The application of coformers in a multicomponent crystal method is one possible strategy to modulate a drug's solubility. A multicomponent crystal is a solid phase formed when several molecules of different substances crystallize in a crystal lattice with a certain stoichiometric ratio. The goal of this review paper is to comprehensively describe the application of coformers in the formation of multicomponent crystals as solutions for pharmaceutically active ingredients with limited solubility. Owing to their benefits including improved physicochemical profile of pharmaceutically active ingredients, multicomponent crystal methods are predicted to become increasingly prevalent in the development of active drug ingredients in the future.


Assuntos
Água , Cristalização/métodos , Solubilidade , Disponibilidade Biológica , Preparações Farmacêuticas
6.
Biol Pharm Bull ; 45(11): 1660-1668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36328502

RESUMO

Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed. Genome-editing technology using Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas9) system is expected to be a therapeutic approach to treat genetic diseases, such as ATTR amyloidosis caused by a point mutation in TTR gene. Previously, we reported that glucuronylglucosyl-ß-cyclodextrin conjugated with a polyamidoamine dendrimer (CDE) had excellent gene transfer ability and that underlying dendrimer inhibited TTR aggregation. Conversely, folate receptors are known to be highly expressed in retina; thus, folate has potential as a retinal target ligand. In this study, we prepared a novel folate-modified CDE (FP-CDE) and investigated its potential as a carrier for the retinal delivery of TTR-CRISPR plasmid DNA (pDNA). The results suggested that FP-CDE/TTR-CRISPR pDNA could be taken up by retinal pigment epithelial cells via folate receptors, exhibited TTR V30M amyloid inhibitory effect, and suppressed TTR production via the genome editing effect (knockout of TTR gene). Thus, FP-CDE may be useful as a novel therapeutic TTR-CRISPR pDNA carrier in the treatment of ATTR ocular amyloidosis.


Assuntos
Neuropatias Amiloides Familiares , Dendrímeros , Humanos , Pré-Albumina/genética , Pré-Albumina/metabolismo , Estudos de Viabilidade , Neuropatias Amiloides Familiares/tratamento farmacológico , Amiloide , Plasmídeos/genética , Ácido Fólico , Pigmentos da Retina/uso terapêutico
7.
ACS Macro Lett ; 11(11): 1225-1229, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36215131

RESUMO

To achieve a systemic targeted delivery of siRNA using polymeric carriers, there is a dilemma between ligand modification and stabilization of the polyplex. Namely, ligand modification often leads to destabilization of the polyplex in the blood circulation. In fact, we previously developed cyclodextrin (CD)/polyamidoamine dendrimer conjugates (CDE) as siRNA carriers, and the interaction of CDE/siRNA was decreased by the conjugation with folate-polyethylene glycol, leading to the destabilization. To overcome this dilemma, in this study, folate-appended polyrotaxanes (Fol-PRX) were developed. Fol-PRX stabilized CDE/siRNA polyplex by intermolecularly connecting CDE molecules through a host-guest interaction between adamantane at the terminals of Fol-PRX and ß-CD in the polyplex. Moreover, the intermolecular connection of the polyplex with Fol-PRX provided movable folate moieties on the surface. As a result, Fol-PRXs enhanced the in vivo antitumor activity of the polyplex after intravenous administration, suggesting their utility as the dual-functional materials for systemic delivery of siRNA polyplexes.


Assuntos
Rotaxanos , RNA Interferente Pequeno , Ácido Fólico , Ligantes , Polietilenoglicóis
8.
Drug Deliv ; 29(1): 2959-2970, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36085575

RESUMO

Lung cancer is the second most common type of cancer after breast cancer. It ranks first in terms of mortality rate among all types of cancer. Lung cancer therapies are still being developed, one of which makes use of nanoparticle technology. However, conjugation with specific ligands capable of delivering drugs more precisely to cancer sites is still required to enhance nanoparticle targeting performance. Monoclonal antibodies are one type of mediator that can actively target nanoparticles. Due to the large number of antigens on the surface of cancer cells, monoclonal antibodies are widely used to deliver nanoparticles and improve drug targeting to cancer cells. Unfortunately, these antibodies have some drawbacks, such as rapid elimination, which results in a short half-life and ineffective dose. As a result, many of them are formulated in nanoparticles to minimize their major drawbacks and enhance drug targeting. This review summarizes and discusses articles on developing and applying various types of monoclonal antibody ligand nanoparticles as lung cancer target drugs. This review will serve as a guide for the choice of nanoparticle systems containing monoclonal antibody ligands for drug delivery in lung cancer therapy.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Nanopartículas , Anticorpos Monoclonais , Humanos , Ligantes , Neoplasias Pulmonares/tratamento farmacológico
9.
Pharmaceutics ; 14(8)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36015335

RESUMO

Recurrent aphthous stomatitis (RAS) is a prevalent clinical disorder that causes mouth ulcers. Furthermore, corticosteroid treatment has been widely utilized for RAS therapy; however, it has side effects on the oral mucosa that limit its application. This study aimed to develop a novel RAS therapy with the natural ingredient α-mangostin, delivered by alginate and chitosan polymers-based hydrogel film (α-M Alg/Chi-HF). To prepare α-M Alg/Chi-HF, the solvent evaporation and casting methods were used, then characterized by using SEM, FTIR, and XRD. Based on the characterization studies, the α-M in α-M/EtOH Alg/Chi-HF with ethanol (EtOH) was found to be more homogenous compared to α-M in Alg/Chi-HF with distilled water (H2O) as a casting solvent. The in vitro viability study using NIH3T3 cells showed 100% viability of α-M Alg/Chi-HF (EtOH) and Alg/Chi-HF after 24 h incubation, indicating well tolerability of these hydrogel films. Interestingly, the in vivo studies using male white rats (Rattus norvegicus Berkenhout) proved that α-M/EtOH Alg/Chi-HF with a recovery of 81.47 ± 0.09% in seven days significantly more effective RAS therapy compared to control. These results suggest that α-M/EtOH Alg/Chi-HF has the potential as an alternative for RAS therapy.

10.
Polymers (Basel) ; 14(16)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36015667

RESUMO

Cancer is the most common cause of death worldwide; therefore, there is a need to discover novel treatment modalities to combat it. One of the cancer treatments is nanoparticle technology. Currently, nanoparticles have been modified to have desirable pharmacological effects by using chemical ligands that bind with their specific receptors on the surface of malignant cells. Chemical grafting of chitosan nanoparticles with hyaluronic acid as a targeted ligand can become an attractive alternative for active targeting. Hence, these nanoparticles can control drug release with pH- responsive stimuli, and high selectivity of hyaluronic acid to CD44 receptors makes these nanoparticles accumulate more inside cells that overexpress these receptors (cancer cells). In this context, we discuss the benefits and recent findings of developing and utilizing chitosan-hyaluronic acid nanoparticles against distinct forms of cancer malignancy. From here we know that chitosan-hyaluronic acid nanoparticles (CHA-Np) can produce a nanoparticle system with good characteristics, effectiveness, and a good active targeting on various types of cancer cells. Therefore, this system is a good candidate for targeted drug delivery for cancer therapy, anticipating that CHA-Np could be further developed for various cancer therapy applications.

11.
Polymers (Basel) ; 14(13)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35808792

RESUMO

Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10-30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.

12.
Pharmaceutics ; 13(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34959275

RESUMO

Natural compounds are emerging as effective agents for the treatment of malignant diseases. The active constituent of α-mangostin from the pericarp of Garcinia mangostana L. has earned significant interest as a plant base compound with anticancer properties. Despite α-mangostin's superior properties as an anticancer agent, its applications are limited due to its poor solubility and physicochemical stability, rapid systemic clearance, and low cellular uptake. Our review aimed to summarize and discuss the nanoparticle formulations of α-mangostin for cancer drug delivery systems from published papers recorded in Scopus, PubMed, and Google Scholar. We investigated various types of α-mangostin nanoformulations to improve its anticancer efficacy by improving bioavailability, cellular uptake, and localization to specific areas These nanoformulations include nanofibers, lipid carrier nanostructures, solid lipid nanoparticles, polymeric nanoparticles, nanomicelles, liposomes, and gold nanoparticles. Notably, polymeric nanoparticles and nanomicelles can increase the accumulation of α-mangostin into tumors and inhibit tumor growth in vivo. In addition, polymeric nanoparticles with the addition of target ligands can increase the cellular uptake of α-mangostin. In conclusion, nanoformulations of α-mangostin are a promising tool to enhance the cellular uptake, accumulation in cancer cells, and the efficacy of α-mangostin as a candidate for anticancer drugs.

13.
Drug Des Devel Ther ; 15: 4213-4226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675484

RESUMO

BACKGROUND: Ulvan is a natural polymer and type of sulfated polysaccharides from green seaweed that could have potential as a candidate for wound dressing material based on the support of its biopolymer characteristics such as antioxidant and antimicrobial activities. OBJECTIVE: In this study, we developed and prepared three different hydrogel films to explore the potency of ulvan for wound dressing application. METHODS: Ulvan hydrogel films were prepared by the facile method through ionic crosslinking with boric acid and added glycerol as a plasticizer. The films were evaluated in regard to swelling degree, water vapor transmission (WVTR), Fourier transform infrared (FTIR), powder x-ray diffractometry (P-XRD), scanning electron microscopy (SEM), mechanical properties, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), antimicrobial, and antioxidant activity. RESULTS: The hydrogel films showed that the different concentration of ulvan in the formula affects the characteristics of the hydrogel film. The higher the concentration of ulvan in UHF, the higher the value of viscosity (201±13.45 to 689±62.23 cps for UHF5 to UHF10), swelling degree (82% to 130% for UHF5 to UHF10 at 1 h), moisture content (24%±1.94% to 18.4%±0.51 for UHF5 to UHF10), and the WVTR were obtained in the range 1856-2590g/m2/24h. Meanwhile, the SEM showed porous hydrogel film. Besides, all hydrogel films can reduce hydroxyl radicals and inhibit gram-positive and negative bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus epidermidis). CONCLUSION: The swelling behavior and WVTR of these films are great and could have potential as a wound dressing biomaterial, supported by their antimicrobial and antioxidant properties.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bandagens , Polissacarídeos/farmacologia , Antibacterianos/administração & dosagem , Antioxidantes/administração & dosagem , Ácidos Bóricos/química , Química Farmacêutica , Reagentes de Ligações Cruzadas/química , Glicerol/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hidrogéis , Plastificantes/química , Polissacarídeos/administração & dosagem , Viscosidade , Cicatrização/efeitos dos fármacos
14.
Polymers (Basel) ; 13(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502930

RESUMO

α-Mangostin (α-M) has various biological activities, such as anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant. However, it has very low solubility in water. The formulation of this compound requires high amounts of solubilizers, which limits its clinical application. In addition, its low solubility in water is a barrier to the distribution of this drug, thus affecting its potency. Cyclodextrin (CD) is widely used as a solubility enhancer of poorly soluble drugs. This study aimed to increase the solubility of α-M in water through complex formation with CD. The complex of α-Mangostin and γ-Cyclodextrin (α-M/γ-CD CX) was prepared by the solubilization method, resulting in a solubility improvement of α-M in water. Characterization of α-M/γ-CD CX by using FTIR-Spectrometry, XRD, H-, C-, and HMBC-NMR showed that α-M was able to form an inclusion complex with γ-CD. The complex yielded an entrapment efficiency of 84.25 and the thermodynamic study showed that the α-M/γ-CD CX was formed spontaneously, based on the negative values of Gibbs energy and ΔH. Interestingly, the solubility of α-M/γ-CD CX significantly increased by 31.74-fold compared with α-M. These results suggest that α-M/γ-CD CX has the potential in the formulation of water-based preparation for clinical applications.

15.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199586

RESUMO

Natural polymer is a frequently used polymer in various food applications and pharmaceutical formulations due to its benefits and its biocompatibility compared to synthetic polymers. One of the natural polymer groups (i.e., polysaccharide) does not only function as an additive in pharmaceutical preparations, but also as an active ingredient with pharmacological effects. In addition, several natural polymers offer potential distinct applications in gene delivery and genetic engineering. However, some of these polymers have drawbacks, such as their lack of water retention and elasticity. Sacran, one of the high-molecular-weight natural polysaccharides (megamolecular polysaccharides) derived from Aphanothece sacrum (A. sacrum), has good water retention and elasticity. Historically, sacran has been used as a dietary food. Moreover, sacran can be applied in biomedical fields as an active material, excipient, and genetic engineering material. This article discusses the characteristics, extraction, isolation procedures, and the use of sacran in food and biomedical applications.


Assuntos
Cianobactérias/química , Polissacarídeos/química , Animais , Indústria Farmacêutica , Elasticidade , Indústria Alimentícia , Humanos
16.
Polymers (Basel) ; 13(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064093

RESUMO

α-mangostin (αM), a xanthone derivative compound isolated from the extract of mangosteen pericarp (Garcinia mangostana L), has potential anticancer properties for breast cancer. However, it has poor solubility in water and low selectivity towards cancer cells. The polymeric nanoparticle formulation approach can be used to overcome these problems. In this study, a chitosan biopolymer-based αM polymeric nanoparticle formulation was encapsulated using kappa carrageenan (αM-Ch/Cr) as a novel carrier for breast cancer therapy and evaluated for their physicochemical properties, drug release profile, and in vitro cytotoxicity against breast cancer cells (MCF-7). Polymeric nanoparticles formulated with varying concentrations of kappa carrageenan were successfully prepared by ionic gelation and spray pyrolysis techniques. αM-Ch/Cr nanoparticles formed perfectly round particles with a size of 200-400 nm and entrapment efficiency ≥ 98%. In vitro release studies confirmed that αM-Ch/Cr nanoparticles had a sustained release system profile. Interestingly, the formulation of polymeric nanoparticles significantly (p < 0.05) increased the cytotoxicity of αM against MCF-7 cell with IC50 value of 4.7 µg/mL compared to the non-nanoparticle with IC50 of 8.2 µg/mL. These results indicate that αM-Ch/Cr nanoparticles have the potential to improve the physicochemical properties and cytotoxicity effects of αM compounds as breast cancer therapy agents.

17.
Chem Pharm Bull (Tokyo) ; 68(11): 1117-1120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132380

RESUMO

Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity. Among 11 CyDs, sulfobutylether (SBE)-ß-CyD showed the highest solubilizing effect for Zerumbone. Phase solubility diagrams of SBE-ß-CyD/Zerumbone in 10% methanol solution showed AL type, and the stability constant was 756 M-1. SBE-ß-CyD also formed the solid complex with Zerumbone by kneading for 90 min. Importantly, the dissolution rate of Zerumbone was improved by complexation with SBE-ß- and hydroxypropyl (HP)-ß-CyDs, and its supersaturation was maintained for several hours. The solubilizing effects by SBE-ß-CyD was greater than that of HP-ß-CyD. Moreover, SBE-ß-CyD/Zerumbone complex also retained the cytotoxic activity of Zerumbone. These results suggest that CyDs, especially SBE-ß-CyD, were useful to improve the solubility of Zerumbone.


Assuntos
Ciclodextrinas/química , Sesquiterpenos/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Varredura Diferencial de Calorimetria , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Humanos , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Solubilidade
18.
Pharmaceuticals (Basel) ; 13(10)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023196

RESUMO

α-Mangostin (α-M), one of the active compounds in Garcinia mangostana peel, has been effectively used in wound healing. However, its poor solubility in aqueous solution causes low bioavailability for skin ulcers, hindering its application in wound healing. The aim of this study was to improve the solubility of α-M through complex formation with 2-hydroxypropyl-ß-cyclodextrin (α-M/HP-ß-CD CX) and to evaluate the healing activity of the complex. The α-M/HP-ß-CD CX was incorporated in a sodium carboxymethylcellulose hydrogel (α-M/HP-ß-CD CX HG), and the in vivo healing activity was examined in mice. Evaluation of α-M/HP-ß-CD CX HG, including organoleptic evaluation, homogeneity, pH, spreadability, swelling ratio, consistency, scanning electron microscopy (SEM), and in vitro drug release, was carried out. The complex formation of α-M/HP-ß-CD CX was confirmed by FTIR and PXRD analysis. The solubility of the α-M/HP-ß-CD CX in water linearly increased about 11.7-fold compared to α-M alone, and by 3.5-fold compared to the α-M/HP-ß-CD physical mixture (α-M/HP-ß-CD CX PM). The α-M/HP-ß-CD CX HG was homogenous, the pH was found to be in the neutral range, the spread area was 5 cm, and the consistency was stable until 14 days. SEM analysis showed that α-M/HP-ß-CD CX HG surged due to the porous structure of the HG. In addition, in vitro release of α-M from α-M/HP-ß-CD CX HG was considerably increased compared to α-M/HP-ß-CD PM HG and α-M HG. Notably, in vivo evaluation in mice showed that α-M/HP-ß-CD CX HG significantly accelerated the wound healing ability compared to other HGs. Thus, α-M/HP-ß-CD CX HG has potential as a new formulation of α-M for wound healing therapy.

19.
Drug Des Devel Ther ; 14: 4387-4405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116423

RESUMO

Colorectal cancer is one of the most common cancer diseases with the increase of cases prevalence >5% every year. Multidrug resistance mechanisms and non-localized therapy become primary problems of chemotherapy drugs for curing colorectal cancer disease. Therefore, the enteric-coated nanoparticle system has been studied and proved to be able to resolve those problems with good performance for colorectal cancer. The highlight of our review aims to summarize and discuss the enteric-coated nanoparticle drug delivery system specific for colorectal cancer disease. The main and supporting literatures were collected from published research articles of journals indexed in Scopus and PubMed databases. In the oral route of administration, Eudragit pH-sensitive copolymer as a coating agent prevents the degradation of the nanoparticle system from the gastric fluid and releases drug to intestinal-colon track. Therefore, it provides a colon-specific targeting ability. Impressively, enteric-coated nanoparticles having a sustained release profile significantly increase the cytotoxic effect of chemotherapeutic drugs and achieve cell-specific target delivery. The enteric-coated nanoparticle drug delivery system represents an excellent modification to improve the effectiveness and performance of anticancer drugs for colorectal cancer disease in terms of the oral route of administration.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Comprimidos com Revestimento Entérico , Administração Oral , Animais , Antineoplásicos/química , Liberação Controlada de Fármacos , Humanos , Nanopartículas
20.
J Adv Pharm Technol Res ; 11(2): 74-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32587820

RESUMO

Epidermal growth factor (EGF) accelerates epidermal regeneration, and it is widely studied as a wound-healing agent. However, the special carrier for the topical administration of EGF is urgently needed to deliver EGF on the wound site. In a preceding study, sacran hydrogel film (Sac-HF) showed a possible use as a dressing material for wound healing, as well as a good capability as a drug carrier. In the current study, we prepared Sac-HF containing EGF (Sac/EGF-HF) and then characterized their physicochemical properties, including thickness, swelling ratio, degradability, tensile strength, and morphology. In addition, we have also conducted thermal and crystallography studies using differential scanning calorimetry (DSC) and X-ray diffraction, respectively. Furthermore, we investigated the in vitro influence of Sac/EGF-HF on cell migration using a fibroblast cell line. Morphology study confirmed that the casting method used for the film preparation resulted in a homogeneous film of Sac/EGF-HF. Furthermore, EGF significantly increased the thickness, tensile strength, and degradability of Sac/EGF-HF compared to Sac-HF. Sac/EGF-HF had a lower swelling ability compared to Sac-HF; this result corroborated the tensile strength result. Interestingly, X-ray diffraction and DSC results showed that Sac/EGF-HF had an amorphous shape. The in vitro studies revealed that Sac/EGF-HF induced the fibroblast migration activity. These results conclude that Sac/EGF-HF has the potential properties of HF for biomedical applications.

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