Development of Raloxifene Hydrochloride Loaded mPEG-PLA Nanoparticles for Oral Delivery

Abstract

Objectives: Raloxifene hydrochloride is used in the treatment of breast cancer which suffers from poor bioavailability problem i.e., only 2% due to excessive first pass metabolism. Development of a delivery system to overcome its bioavailability problem can be done by using mPEG-PLA polymeric nanoparticles which has many scientific applications. Methods: mPEG-PLA polymer has been prepared and evaluated using NMR, FTIR and GPC. Nanoparticles were prepared using emulsion-diffusion-evaporation technique and drug release patterns were evaluated. Pharmacokinetic study was done using Sprague dawley rats to increase the drugs bioavailability. Analytical method was developed with an LOQ 0.5 µg/ml and LOD 0.167 µg/ml. Results: Nanoparticles were formulated using synthesized mPEG-PLA polymer has a particle size range of 165-180 nm. In vitro release study showed, about 72% of drug was released from nanoparticles over the given time duration and showed sustained release for 20 days following Higuchi kinetics. Pharmacokinetic study showed that drug loaded nanoparticles were having approximately 4.87 times more bioavailability than the free drug. Conclusion: Raloxifene hydrochloride loaded nanoparticles prepared with the synthesized mPEG-PLA polymer which can release the drug slowly and were suitable for oral delivery. From pharmacokinetic study, it was observed that raloxifene hydrochloride loaded nanoparticles were found to show an increase of relative oral bioavailability to that of raloxifene hydrochloride suspension.

Nanomedicine for increasing the oral bioavailability of cancer treatments

“…However, when designed for oral administration, they are affected by low GIT absorption, poor mucus penetration, and rapid elimination, though optimizing the surface chemistry of PLA nanoparticles with cell-penetrating peptides [ 59 ] can mitigate these drawbacks. Similar benefits are achieved with PLA nanoparticle PEGylation, as demonstrated by the significantly increased bioavailability of encapsulated raloxifene hydrochloride compared to the free administered drug [ 60 ], potentially enhancing the usability of this therapeutic for breast cancer prevention [ 61 ].…”

“… 1. Polymers Carnitine coated PLGA NP – Increased paclitaxel BA [ 58 ] Chitosan coated PLGA NP Oral mucositis induced by chemotherapy Increased oral cavity residence time [ 118 ] PLGA NP Oral cavity cancer Increased local docetaxel delivery [ 119 ] Pegylated PLA NP Breast cancer prevention Increased raloxifene hydrochloride BA [ 60 , 61 ] Pegylated PLA NP Lung cancer Increased paclitaxel BA [ 63 ] Hyaluronic acid coated pegylated PLGA NP Colon cancer Increased PTC209 delivery and Inhibited cancer stem cell proliferation [ 123 ] PCL NP – Increased ellagic acid [ 67 ] 2. Inorganic materials Aluminum silicate – Increased methotrexate release properties [ 64 ] Selenium NP Prostate cancer Reduced side effects and increased tumor growth inhibition [ 67 ] 3.…”

Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

“…It is possible to use alternate processing and speci c formulation techniques if these properties prevent the development of a drug formulation [15,16]. Through the oral route, As a result of nanotechnology, the limitations of conventional capsules overcame by presenting the medications as polymeric nanoparticles [17], nanocrystals [18,5], peptide nanoparticles [19], nano-micelles [20], liposomes [21,22] etc. To circumvent the issues discussed previously, liposomal formulations are being considered as potential substitutes for increasing NE's oral bioavailability [12] [23].…”