Lipid-based nanocarriers for oral delivery of peptides

Therapeutic peptides can treat a wide variety of diseases with selective and potent action. Their oral bioavailability is strongly limited by an important proteolytic activity in the intestinal lumen and poor permeation across the intestinal border. We have evaluated the capacity of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to overcome both oral bioavailability limiting aspects, using leuprolide (LEU) as model peptide. Lipidization of LEU by formation of a hydrophobic ion pair (HIP) with sodium docusate enables a significant increase of peptide encapsulation efficiency in both SLN and NLC. The nanocarriers, obtained by high-pressure homogenization, measured 120 nm and were platelet shaped. Regarding the protective effect towards proteolytic degradation, only NLC maintained LEU integrity in presence of trypsin. Intestinal transport, evaluated on Caco-2 (enterocyte-like model) and Caco-2/HT29-MTX (mucin-secreting model) monolayers, showed nanocarriers internalization by enterocytes but no improvement of LEU permeability. Indeed, the combination of nanoparticles platelet-shape with the poor stability of the HIP in the transport medium induces a high burst release of the peptide, limiting nanoparticles capacity to transport LEU across the intestinal border. Stability of peptide lipidization needs to be improved to withstand biorelevant medium to benefit from the advantages of encapsulation in solid lipid nanocarriers and consequently improve their oral bioavailability.

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Solid lipid nanocarriers as alternative drug delivery system for improved oral delivery of drugs

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6-s.4410 ◽

2020 ◽

Vol 10 (6-s) ◽

pp. 168-172

Author(s):

Gorre Thirupathi ◽

Samanthula Kumara Swamy ◽

Alli Ramesh

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Lipid Nanoparticles ◽

Delivery Systems ◽

Chemical Degradation ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Lipid Nanocarriers ◽

Pass Metabolism

Oral bioavailability of drugs is mainly limited due to the poor aqueous solubility, enhanced chemical degradation, reduced permeation and/or first pass metabolism. Various novel delivery systems are developed for improved oral bioavailability of these drugs such as modified orals, buccal, transdermal and osmotic delivery systems. Colloidal carrier systems such as nanoparticles, lipid nanoparticles, nanoemulsions, microspheres, liposomes, resealed erythrocytes and transfersomes were also developed to enhance the oral delivery. Among these, solid lipid nanocarriers (SLNs) also gain much attention on the enhancement of oral bioavailability. SLNs are submicron sized nanoparticles and composed of solid lipid, surfactants and cosurfactants. The enhanced oral bioavailability of poorly soluble drugs from SLNs might be due to the reduced particle size, bypassed presystemic metabolism, and enhanced gastric mucosa permeability. Vast literature is available for the advantages, limitations, preparation methods, evaluation parameters and application of SLNs in different routes. This review mainly focused on list of drugs developed as SLNs and considered as an alternative approach to enhance the oral bioavailability based on pharmacokinetic as well as pharmacodyanmic parameters was discussed. Keywords: Oral bioavailability, solubility, first-pass metabolism, solid lipid nanoparticles, pharmacokinetics, pharmacodynamics.

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Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

Asian Journal of Pharmacy and Technology ◽

10.52711/2231-5713.2021.00016 ◽

2021 ◽

pp. 97-104

Author(s):

Kumara Swamy S ◽

Ramesh Alli

Keyword(s):

Drug Release ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Delivery ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Sustained Drug Release ◽

Bioavailability Enhancement ◽

Solid Lipid

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

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Development of Lipid-Based Nanocarriers for Increasing Gastrointestinal Absorption of Lupinifolin

Planta Medica ◽

10.1055/a-1095-1129 ◽

2020 ◽

Vol 86 (05) ◽

pp. 364-372 ◽

Cited By ~ 1

Author(s):

Jidapa Musika ◽

Nuannoi Chudapongse

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Medium Chain Triglyceride ◽

Lipid Nanoparticles ◽

Delivery Systems ◽

Nanostructured Lipid Carriers ◽

Gastrointestinal Absorption ◽

Prolonged Release ◽

Solid Lipid ◽

Lipid Nanocarriers

AbstractLupinifolin, a plant flavonoid, has been reported to possess various pharmacological effects. It most likely exerts low oral bioavailability because of poor water solubility. The objective of this study was to develop lipid nanocarriers as drug delivery systems to increase the gastrointestinal absorption of lupinifolin extracted from Albizia myriophylla. Three types of nanocarriers, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were prepared by an emulsification-sonication technique. All three types of nanocarriers loaded with lupinifolin, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were successfully synthesized. The lipid components chosen to formulate nanocarriers were tripalmitin and/or medium chain triglyceride. Physicochemical characterizations along with releasing profiles of lupinifolin-loaded lipid nanocarriers were compared. It was found that the best lipid nanocarrier for lupinifolin was lupinifolin-loaded nanostructured lipid carriers, which demonstrated the particle size of 151.5 ± 0.1 nm, monodispersity distribution with a polydispersity index of 0.24, negative surface charge at − 41.2 ± 0.7 mV, high encapsulation (99.3%), and high loading capacity (5.0%). The obtained lupinifolin-loaded nanostructured lipid carriers exhibited prolonged release in a simulated circulatory system but produced a low release in gastrointestinal conditions (3.7%). Intestinal permeability of the nanocarriers was further evaluated in everted intestinal sacs. The results from the ex vivo study indicated that lupinifolin-loaded nanostructured lipid carriers significantly increased the absorption of lupinifolin compared to the native form. In conclusion, lupinifolin-loaded lipid nanocarriers were successfully formulated as delivery systems to enhance its oral bioavailability. Further in vivo experiments are needed to validate the results from this study.

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Improved oral bioavailability of docetaxel by nanostructured lipid carriers: in vitro characteristics, in vivo evaluation and intestinal transport studies

RSC Advances ◽

10.1039/c5ra14588k ◽

2015 ◽

Vol 5 (117) ◽

pp. 96437-96447 ◽

Cited By ~ 21

Author(s):

Guihua Fang ◽

Bo Tang ◽

Yanhui Chao ◽

Yu Zhang ◽

Hui Xu ◽

...

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Intestinal Transport ◽

Nanostructured Lipid Carriers ◽

Absorption Mechanism ◽

In Vivo Evaluation ◽

Transport Studies

The objective of the current study was to explore the potential of nanostructured lipid carriers (NLC) for oral delivery of docetaxel (DTX) and investigate the absorption mechanismin vivo.

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Lacidipine Loaded Solid Lipid Nanoparticles for Oral Delivery: Preparation, Characterization and In vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2016.9.6.2 ◽

2016 ◽

Vol 9 (6) ◽

pp. 3524-3530 ◽

Cited By ~ 1

Author(s):

Kishan V. ◽

Sandeep V ◽

Narendar D ◽

Arjun N

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Delivery ◽

Lipid Nanoparticles ◽

Pharmacokinetic Studies ◽

Electron Microscopic ◽

In Vivo Evaluation ◽

Solid Lipid

The objective of this study was to develop and evaluate lacidipine (LD) loaded solid lipid nanoparticles (LD-SLNs) for improving the oral bioavailability. LD-SLNs were prepared in two steps. First step was hot homogenization and next by ultrasonication method, using triglycerides (tripalmitin and tristearin), monoglyceride and surfactants (Poloxamer 188 and egg lecithin E80). The prepared LD-SLNs were characterized for particle size, PDI, zeta potential, drug content, entrapment efficiency (EE %). In vitro drug release studies using a dialysis bag method in 0.1N HCl and pH 6.8 phosphate buffer were conducted. In addition, long-term physical stability of the optimized SLNs was investigated at refrigerated and room temperature for 60 days. FTIR and DSC studies revealed that no interaction between the drug and lipids. LD-SLNs prepared with Dynasan-116 (F3), having the size of 141.86nm, PDI of 0.293, ZP of -22.3 m with 94.75% of EE was optimized and was stable for 60days. Scanning electron microscopic studies showed nearly spherical shaped particles. Further, pharmacokinetic studies were conducted in wistar rats. The relative bioavailability of LD in SLNs was 2.03 times when compared with that of the LD suspension. The results are indicative of SLNs as suitable lipid based carrier system for improving the oral bioavailability of LD.

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Targeted solid lipid nanoparticles with peptide ligand for oral delivery of atorvastatin calcium

RSC Advances ◽

10.1039/c6ra02371a ◽

2016 ◽

Vol 6 (42) ◽

pp. 35901-35909 ◽

Cited By ~ 8

Author(s):

Qingqing Tian ◽

Fang Ding ◽

Lingling Guo ◽

Jing Wang ◽

Fanhong Wu ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Delivery ◽

Lipid Nanoparticles ◽

Peptide Ligand ◽

Atorvastatin Calcium ◽

Solid Lipid

Designing feasible and effective peptide ligand-modified solid lipid nanoparticles (SLNs) to improve the oral bioavailability of atorvastatin calcium (ATC).

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Solid Lipid Nanoparticles of Dronedarone Hydrochloride for Oral Delivery: Optimization, In Vivo Pharmacokinetics and Uptake Studies

Pharmaceutical Nanotechnology ◽

10.2174/2211738507666190802140607 ◽

2019 ◽

Vol 7 (5) ◽

pp. 375-388 ◽

Cited By ~ 2

Author(s):

Vaishali M. Gambhire ◽

Makarand S. Gambhire ◽

Nisharani S. Ranpise

Keyword(s):

Particle Size ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Delivery ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Pharmacokinetic Studies ◽

Solid Lipid

Background: Dronedarone HCl (DRD), owing to its poor aqueous solubility and extensive presystemic metabolism shows low oral bioavailability of about 4% without food, which increases to approximately 15% when administered with a high fat meal. Objective: Solid lipid nanoparticles (SLN) were designed with glyceryl monstearate (GMS) in order to improve oral bioavailability of DRD. Methods: Hot homogenization followed by probe sonication was used to prepare SLN dispersions. Box-Behnken design was used to optimize manufacturing conditions. SLN were characterized for particle size, zeta potential, entrapment efficiency, physical state and in vitro drug release. Pharmacokinetics and intestinal uptake study of dronedarone HCl loaded solid lipid nanoparticles (DRD-SLN) in the presence and absence of endocytic uptake inhibitor, chlorpromazine (CPZ) was performed with conscious male Wistar rats. Results: Optimized formulation of SLN showed particle size of 233 ± 42 nm and entrapment efficiency of 87.4 ± 1.29%. Results of pharmacokinetic studies revealed enhancement of bioavailability of DRD by 2.68 folds from SLN as compared to DRD suspension. Significantly reduced bioavailability of DRD-SLNs in the presence of chlorpromazine, demonstrated the role of endocytosis in uptake of SLN formulation. Conclusion: These results indicated that dronedarone HCl loaded SLN could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first pass metabolism.

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Enhancement of Oral Bioavailability of Puerarin by Polybutylcyanoacrylate Nanoparticles

Journal of Nanomaterials ◽

10.1155/2011/126562 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Lixia Zhao ◽

Anchang Liu ◽

Min Sun ◽

Jinsong Gu ◽

Haigang Wang ◽

...

Keyword(s):

Zeta Potential ◽

Oral Bioavailability ◽

Oral Delivery ◽

Drug Carrier ◽

In Vitro Release ◽

Spherical Shape ◽

Oral Drug ◽

Burst Release ◽

Vitro Release

The interest using novel drug delivery systems to improve oral bioavailability of drug with poor solubility is increasing. In this study, a new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of puerarin (PUE). PUE-loaded PBCN was successfully prepared by anionic polymerization method. Characterization of PUE-loaded PBCN was evaluated with morphology, size, zeta potential, and in vitro release study. The PBCN loading PUE exhibited a spherical shape under transmission electron microscopy with an average size of 159.4 nm, and the zeta potential was −15.0 mV. The in vitro release of PUE-loaded PBCN showed an initial burst release followed by a sustained release. Physicochemical state of PUE in PBCN was investigated by differential scanning colorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. The results indicated that PUE in PBCN was in a noncrystalline state. The oral pharmacokinetic study in rats showed that the relative bioavailability of PUE-encapsulated PBCN to the crude PUE was more than 550%. It can be concluded that PBCN as an oral drug carrier can significantly improve the oral bioavailability of PUE.

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