جستجوی مقالات مرتبط با کلیدواژه « nanostructured lipid carriers » در نشریات گروه « پزشکی »

Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.

Hirsutism is characterized by the excessive growth of coarse hair in women, resembling the typical pattern seen in men. It affects between 5 to 10 % of females of reproductive age. Excessive hair growth often leads to significant mental and emotional anguish. Hirsutism is the result of an overabundance of androgens being secreted by the ovaries or adrenal glands. This article offers a comprehensive review of numerous causes that might provoke hirsutism which includes polycystic ovarian syndrome, Cushing syndrome, idiopathic hirsutism, insulin resistance, congenital adrenal hyperplasia, ovarian or adrenal tumors, menopause, and the use of certain drugs. Polycystic ovary syndrome and ovarian tumors are frequent underlying factors of hyperandrogenism, which subsequently results in the development of Hirsutism. Mechanical and cosmetic hair removal methods are viable options for managing hirsutism. This study examines the pharmacological therapies that have proven essential in enhancing the quality of life for patients. These treatments include oral contraceptives, antiandrogen therapy like spironolactone, cyproterone acetate, flutamide, and finasteride, specific insulin-lowering medicines, gonadotrophin-releasing hormone agonists, and topical treatment such eflornithine hydrochloride cream (13.9% w/w cream). This review also explored significance of nanotechnology-based methods like nanostructured lipid carriers, solid lipid nanoparticles, liposomes, cerosomes, and nanogel in enhancing the effectiveness of medications used to treat hirsutism. A comprehensive update has been made to the latest information on clinical studies and patents linked to the treatment of hirsutism.

 Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration.

 NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel.

 Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels.

 Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

Brain, predisposed to local and metastasized tumors, has always been the focus of oncological studies. Glioblastoma multiforme (GBM), the most common invasive primary tumor of the brain, is responsible for 4% of all cancer-related deaths worldwide. Despite novel technologies, the average survival rate is 2 years. Physiological barriers such as blood-brain barrier (BBB) prevent drug molecules penetration into brain. Most of the pharmaceuticals present in the market cannot infiltrate BBB to have their maximum efficacy and this in turn imposes a major challenge. This mini review discusses GBM and physiological and biological barriers for anticancer drug delivery, challenges for drug delivery across BBB, drug delivery strategies focusing on SLNs and NLCs and their medical applications in on-going clinical trials. Numerous nanomedicines with various characteristics have been introduced in the last decades to overcome the delivery challenge. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were introduced as oral drug delivery nanomedicines which can be encapsulated by both hydrophilic and lipophilic pharmaceutical compounds. Their biocompatibility, biodegradability, lower toxicity and side effects, enhanced bioavailability, solubility and permeability, prolonged half-life and stability and finally tissue-targeted drug delivery makes them unique among all.

The aim of this study was to characterize the undecylenoyl phenylalanine (Sepiwhite (SEPI))-loaded nanostructured lipid carriers (NLCs) as a new antimelanogenesis compound.

In this study, an optimized SEPI-NLC formulation was prepared and characterized for particle size, zeta potential, stability, and encapsulation efficiency. Then, in vitro drug loading capacity and the release profile of SEPI, and its cytotoxicity were investigated. The ex vivo skin permeation and the anti-tyrosinase activity of SEPI-NLCs were also evaluated.

The optimized SEPI-NLC formulation showed the size of 180.1 ± 5.01 nm, a spherical morphology under TEM, entrapment efficiency of 90.81 ± 3.75%, and stability for 9 months at room temperature. The differential scanning calorimetry (DSC) analysis exhibited an amorphous state of SEPI in NLCs. In addition, the release study demonstrated that SEPI-NLCs had a biphasic release outline with an initial burst release compared to SEPI-EMULSION. About 65% of SEPI was released from SEPI-NLC within 72 h, while in SEPI-EMULSION, this value was 23%. The ex vivo permeation profiles revealed that the higher SEPI accumulation in the skin following application of SEPI-NLC (up to 88.8%) compared to SEPI-EMULSION (65%) and SEPI-ETHANOL (74.8%) formulations (P < 0.01). An inhibition rate of 72% and 65% was obtained for mushroom and cellular tyrosinase activity of SEPI, respectively. Moreover, results of in vitro cytotoxicity assay confirmed SEPI-NLCs to be non-toxic and safe for topical use.

The results of this study demonstrate that NLC can efficiently deliver SEPI into the skin, which has a promise for topical treatment of hyperpigmentation.

This study was proposed to assess the potential role of efflux transporters in reversing fluconazole resistance in Candida glabrata isolates treated with fluconazole loaded nanostructured lipid carriers (FLZ-NLCs).

The ultrasound technique was used to synthesize the FLZ-NLCs. Four fluconazole-resistant, as well as one susceptible standard C. glabrata isolates, were applied and exposed to FLZ/ FLZ-NLCs for 20 h at 37°C. Real-time PCRs were done to estimate the likely changes in ATP-binding cassette transporter genes.

Similar to the FLZ-exposed-susceptible standard strain which showed no alteration, the genes were not up-regulated significantly under the FLZ-NLCs treated condition. While they were over-expressed when the yeasts were treated with fluconazole.

It is highly suggested that due to the nature of the NLCs which shields the whole conformation of the drug, FLZ is not recognized by the efflux transporter subunits and consequently the translocation would not happen.

To investigate the in vitro anti-skin-aging properties of Cratoxylum formosumextract and encapsulate this plant extract in nanostructured lipid carriers (CFE-NLCs) fordermal application.

The biological properties of the plant extract, including enhanced procollagen typeI synthesis and anti-matrix metalloproteinase activity, were evaluated to assess its cosmeticbenefits. An artificial neural network (ANN) coupled with K-fold cross-validation was appliedto investigate the effects of the formulants and optimize the CFE-NLCs. The physicochemicalproperties, percutaneous absorption, and irritation potential of the CFE-NLCs were analyzed.

Liquid chromatography-mass spectrometry analysis revealed that CFE contained5-O-caffeoylquinic acid as the vital constituent. Appropriate skin-care properties were alsodemonstrated with respect to enhanced type I procollagen synthesis and the inhibition of MMP-1, MMP-3, and MMP-9 in primary human dermal fibroblasts. The optimal CFE-NLCs exhibitedbetter skin absorption and biocompatibility and lower irritation potential than the free botanicalextract solution.

The findings obtained highlight CFE-NLCs as promising skin-care ingredients.

The optimal formulation of Nanostructured lipid carriers (NLCs) that contains argan oil and caffeine was considered to be developed as a topical treatment for hair loss.  26 batches were prepared according to the central composite design. Dynamic light scattering technique showed size, polydispersity index (PDI), and zeta potential, and electron microscopy depicted the morphology of NLCs. Caffeine encapsulation efficiency (EE) was measured by UV/Vis spectroscopy. Fourier-transform infrared spectroscopy (FTIR) was applied to show caffeine and NLCs interactions. The caffeine invivo morin model was designed to determine the caffeine penetration into follicles and stratum corneum.  The optimal formulation consisted of 2% lipid, 2% surfactant, stearic acid/argan oil ratio of 3.5, and span/tween ratio of 1.25. Its spherical NLCs size, PDI, and zeta potential were 256.2 nm, 0.225, and -25.4 respectively. The caffeine EE% was 89% which was homogenously encapsulated in NLCs as shown in FTIR analysis. In vivo studies showed these nanoparticles have the ability to accumulate in the hair follicles by the time.  The NLC formulation optimized in this study is a potential formulation for intrafollicular delivery of caffeine.

Cutaneous leishmaniasis is a global health problem. The discovery of new and highly efficient anti-leishmanial treatments with lower toxicity is globally needed. The current study was carried out to evaluate the anti-leishmanial effects of artemether (ART) and ART-loaded nanostructured lipid carriers (ART-NLCs) against promastigotes and amastigotes of Leishmania major.

Solvent diffusion evaporation technique was applied to prepare ART-NLCs. These nanoparticles were characterized using a particle size analyzer (PSA), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The antiparasitic activity on amastigote was assessed in J774 cell culture. The drug cytotoxicity on promastigote and macrophage was assessed using the MTT technique after 24 and 48 h and compared with NLCs, ART, and amphotericin B, as the control agents. The selectivity index was calculated for the agents.

The DLS and PSA techniques confirmed that ART-NLCs were homogenous in size with an average diameter of 101 ± 2.0 nm and span index of 0.9. The ART-NLCs significantly heighten the antileishmanial activity of ART (P < 0.001). The IC50 values of ART and ART-NLCs on promastigotes after 24 and 48 h were 76.08, 36.71 and 35.14, 14.81 μg/mL, respectively while they were calculated 53.97, 25.43 and 20.13, 11.92 for amastigotes. Also, ART-NLCs had the lowest cytotoxicity against macrophages. Furthermore, among the agents tested, ART-NLCs had the highest selectivity index.

ART-NLCs had lower cytotoxic effects than ART and amphotericin B, also its selectivity index was significantly higher. Based on the findings of the study, this formulation could be a promising candidate for further research into leishmaniasis treatment.

The clinical outcome of anti-HIV therapy is poor due to the inherent fallouts ofanti-HIV therapy. It is further worsened due to the presence of viral reservoirs in immune cellslike the macrophages. An ideal anti-HIV therapy must reach, deliver the drug and exert itsaction inside macrophages. To address this, we developed novel cationic nanostructured lipidcarriers of efavirenz (cationic EFV-NLC).

The developed cationic EFV NLCs were evaluated for particle size, zeta potential,encapsulation efficiency, in-vitro drug release, DSC, XRD, TEM, cytotoxicity, cellular uptakestudies and anti-HIV efficacy in a monocyte-derived macrophage cell line (THP-1).

Cationic EFV-NLCs showed high encapsulation efficiency (90.54 ± 1.7%), uniformparticle size distribution (PDI 0.3-0.5 range) and high colloidal stability with positive zetapotential (+23.86 ± 0.49 mV). DSC and XRD studies confirmed the encapsulation of EFVwithin NLCs. Cytotoxicity studies (MTT assay) revealed excellent cytocompatibility (CC5013.23 ± 0.54 μg/mL). Fluorescence microscopy confirmed the efficient uptake of cationic EFVNLCs,while flow cytometry revealed time and concentration dependant uptake within THP-1cells. Cationic EFV-NLCs showed higher retention and sustained release with 2.32-fold higherpercent inhibition of HIV-1 in infected macrophages as compared to EFV solution at equimolarconcentrations. Interestingly, they demonstrated 1.23-fold superior anti-HIV efficacy over EFVloadedNLCs at equimolar concentrations.

Cationic NLCs were capable of inhibiting the viral replication at higher limitsconsistently for 6 days suggesting successful prevention of HIV-1 replication in infectedmacrophages and thus can prove to be an attractive tool for promising anti-HIV therapy.

Breast cancer therapy has remained as one of the major healthcare challenges. Based on the critical role of cyclin-dependent Kinase 4/6 (CDK 4/6) in cell cycle progression, targeting this signaling appears promising for cancer therapy. Palbociclib, a selective CDKs 4/6 inhibitor, is a first-line treatment for estrogen receptor positive breast cancer, however, poor absorption or side effects may negatively affect its efficiency. This prompted us to incorporate palbociclib into the nanostructured lipid carriers (NLCs) and evaluate the anticancer effect of the nanoformulation (Pa-NLCs) in in vitro and in vivo models of breast cancer. Pa-NLCs were developed by high pressure homogenization followed by assessment of the physicochemical characteristics and bioactivities in MCF-7 breast cancer cells and female Wistar rats exposed to the carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA). The prepared Pa-NLCs demonstrated suitable physicochemical characteristics including the controlled release pattern, efficient cellular uptake, and cytotoxicity, while, free palbociclib failed to show significant effects. Rats treated with Pa-NLCs exhibited significantly reduced tumor volumes, increased survival rates, and histopathological improvement. Free palbociclib was significantly less efficient than Pa-NLCs.Pa-NLCs by improving the pharmacological profile of palbociclib and providing longer-lasting effects can be considered as a promising nanoformulation against the breast cancer.

Topical fungal infections are one of the often faced diseases worldwide. The first choice for the treatment of fungal infection is topical therapy due to its advantages such as decreasing the risk of systemic side effects and targeting the drug at the site of fungal infection. The treatment of the fungal infection depends on the penetration of the drug molecules through the outermost layer of the skin (stratum corneum) at an effective concentration. The disadvantages of topical treatment are its lack of drug adherence at the site of application and bigger particle size of drug molecules. Nanostructured lipid carriers are the advanced form of lipid nanoparticles and carry the nano range of the drug molecules, which helps to achieve localized and slow release. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments, and gels. Several carrier systems loaded with antifungal drugs have shown promising results in the treatment of skin fungal infections.

This study aimed to improve the pharmacokinetic behavior of polyunsaturatedfatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxichydroperoxides, develops off-flavors and shortens shelf-life. Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherolwas successfully prepared by melt blending and hot sonication method to enhance the oxidativestability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stabilityof prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) andthiobarbituric acid (TBA) during 40 days. Electron microscopy and particle size analysis showed dispersed and homogenousNPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longtermstability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days ofstorage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed betteroxidative stability compared with the all other formulations. Also, it was found that the NLC asan encapsulation method was more successful to inhibit the formation of the primary oxidationproducts than the secondary oxidation products. Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherolwithin the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clearbeverages.

Treatment of lung diseases is one of the major healthcare challenges. Ferulic acid (FA), a phenolic compound with well-established antioxidant and anti-inflammatory properties, has shown promising therapeutic potential against the pulmonary disorders; however, low bioavailability may negatively affect its efficiency. This, prompted us to incorporate FA into the nanostructured lipid carriers (FA-NLCs) and evaluate the toxicity of this nanoformulation in human lung adenocarcinoma cell line (A549) and its suitability for pulmonary drug delivery.
FA-NLCs were prepared by high-pressure homogenization followed by assessment of the physicochemical properties of nanoparticles, in vitro release profile, aerosol characteristics, in vitro cytotoxicity, pharmacokinetic parameters and lung deposition of the nanoparticles after nebulization in Balb/c mice.
Formation of FA-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. FA-NLCs exhibited toxic effects on A549 cells for longer time periods as compared to FA solution. Following the aerosolization, suitable aerodynamic properties were obtained and FA-NLCs formulation provided significantly increased residence time and slower lung clearance for FA. Further confocal microscopy visualization confirmed the lung deposition of nanoparticles. Encapsulation of FA into the NLCs resulted in the improved pharmacokinetic parameters in plasma or lung tissue samples.
Application of the aerosolized FA-NLCs formulation which improves the pulmonary bioavailability of FA might result in the increased efficiency and reduced dosing frequency of this phytochemical. In this respect, development of inhalable nano-based drug delivery systems appears as a promising therapeutic approach against the lung disorders.

Nanostructured lipid carriers (NLCs) composed of solid lipid and oil are a new generation of lipid nanoparticles which have exhibited some merits over traditional used lipid nanoparticles in fortifying food and beverages and nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles.
In this study, Precirol and Compritol as solid lipids, Miglyol and Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants were used to prepare vitamin D3-loaded NLC dispersion using hot homogenization method. The particle size and size distribution for all formulations were evaluated by immediately after production and during a storage period of 60 days.
The Precirol-based NLC showed superiority over Compritol-based NLC in the point of physical stability. Results clearly suggested that an optimum concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the surface of nanoparticles effectively and prevent agglomeration during the homogenization process. Octyloctanoat was introduced for the first time as a good substituent for Miglyol in the preparation of NLC formulations. The vitamin D3 Intestinal absorption enhanced by the incorporating in NLCs.
It was concluded that NLC showed a promising approach for fortifying beverages by lipophilic nutraceuticals such as vitamin D.

Hyperpigmentation occurs when melanin is overproduced in certain spots on the skin and is one of the most challenging skin conditions to treat. Although it is usually harmless, for cosmetic reasons, it is dreadfully bothersome to those who undergo it. It was reported that N-acetyl-glucosamine (NAGA) prevents melanin synthesis and alters the expression of numerous genes related to pigmentation. In spite of these advantages, NAGA cannot be employed in topical formulations due to its extremely polar characteristics. Nanoparticles, especially lipid-based ones, have been introduced as an efficient carrier for dermal drug delivery.
The aim of the present study was to load adequate hydrophilic NAGA to the lipophilic nanostructured lipid carriers (NLCs) for potential dermal application. NAGA-loaded NLCs were formulated, using hot homogenization technique, and the characteristics of the optimized formulation were analyzed by laser light scattering, X-ray diffraction, and scanning electron microscopy methods. Loading capacity percentage and in vitro release study were carried out by applying a validated HPLC method. The optimum formulation was utilized for the in vivo skin lightening evaluations in healthy volunteers.
NAGA-loaded NLCs demonstrated promising results (the size of 190 nm, narrow size distribution, loading capacity of 9%, and appropriate NAGA release profile) suitable for dermal delivery. XRD results exhibited a dramatic reduction in the crystalline structure of encapsulated NAGA. Dermoscopy images indicated a considerable decline in melanin distribution pattern in the majority of the cases treated with NAGA-loaded NLCs.
Thus, this study has opened new horizons for the potential use of lipid based nanoparticles in the managing of hyperpigmentation.

During the past decade, pharmaceutical science has seen rapid growth in interest for nanoscale materials. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are popular research topics recently introduced as nano-scale drug carriers; they have shown numerous merits in drug delivery. Size is the most important index in a nanocarrier affecting its drug delivery efficiency. The influence of preparation conditions and type of lipidic components on the size of SLN and NLC in comparable states seems to be interesting for researchers who investigate these types of carriers. This review highlights the results of SLN and NLC particle size and size distribution comparisons.