Polymeric nanoparticles A Novel Approach

POLYMERIC NANOPARTICLES-

A NOVEL APPROACH

Prepared by: Shivam Thakore Guided by: Ms Rudree Pathak Ankit Patel

05/03/2023 1Department of Pharmaceutical Technology,

LJ institute of Pharmacy, Ahmedabad

Table of Contents Introduction Advantages Disadvantages Polymers used Method Of Preparation Characterization Questions that can be asked References

05/03/2023 2Department of Pharmaceutical Technology, LJ

institute of Pharmacy, Ahmedabad

Introduction: Polymeric Nanoparticles• What are PNP’s?

○ They are solid colloidal particles ranging in size from 10 to 1000 nm (1µm).

Drug may be dissolved, entrapped, encapsulated or attached to a nanoparticle matrix .

Because these systems have very high surface areas, drugs may also be adsorbed on their surface.

Polymer-based nanoparticles effectively carry drugs, proteins and DNA to target cells and organs.

Their nanometer-size promotes effective permeation through cell membranes and stability in the blood stream

05/03/2023 3Department of Pharmaceutical Technology, LJ

institute of Pharmacy, Ahmedabad

Depending upon Method

of Preparati

on

Nanospheres

Nanocapsules





Nanocapsules: They are the systems in which the drug is confined to a cavity surrounded by a unique polymer membrane.

Nanospheres: They are the matrix systems in which the drug is physically and uniformly dispersed.



Advantages

Increases the stability of any volatile agents & can be easily and cheaply fabricated in large quantities by a multimethods.

Has significant advantages over traditional oral and intravenous methods of administration in terms of efficiency and effectiveness.

Delivers a higher concentration of pharmaceutical agent.

The choice of polymer and the ability to modify drug release from polymeric nanoparticles have made them ideal candidates for cancer therapy, delivery of vaccines, contraceptives and delivery of targeted antibiotics.



Cont… Targeted Drug Delivery System. Polymeric nanoparticles can be easily incorporated into

other activities related to drug delivery, such as tissue engineering

Other all advantages over single unit dosage forms are as such



Disadvantages

Very costly formulation with no low yield Productivity is more difficult. As a industrial

applications, Technology transfer to commercial production is very difficult.

Reduced ability to adjust the dose Highly sophisticated technology Requires skills to manufacture. Stability of dosage form is big issue owing to its nano

size.



Polymers used in Preparation

Natural Hydrophilic

Proteins

Polysaccharides05/03/2023 10

Department of Pharmaceutical Technology, LJ institute of Pharmacy, Ahmedabad

PROTIENS POLYSACHCHARIDES

Gelatin Alginate

Albumin Dextran

Lectin Chitosan

Legumine Agarose

Viciline Pullulan

PRE-POLYMERIZED POLYMERIZED IN PROCESS

Poly E caprolactone Poly Isobutyrl cyano acrylates (PICA

PLA PBCA

Poly lactide co glycolide (PLGA) PHCA

Polystyrene Poly methyl methacyrlate (PMMA)



Method of Preparation

05/03/2023Department of Pharmaceutical Technology,

LJ institute of Pharmacy, Ahmedabad 12

Polymerization based methods

Polymer precipitation

methods

Amphiphilic

macromolecule cross-

linking



Heat Cross-linking

Chemical Cross-linking

Amphiphilic macromolecule

cross-linking



Polymerization based Methods

Polymerization of monomers Emulsion

polymerization

Interfacial complexat

ion

Dispersion polymerization

Interfacial condensation polymerization



PolymerPrecipitation

methods

Solvent extraction/

evaporation

Solvent displacement

(nanoprecipitation)

Salting out



Amphiphilic Macromolecule cross-linking

Heat / Chemical Cross-Linking



Aq protein (BSA),

Surfactant

Oil

High Pressure Homoginization

W/O emulsion

Centrifugation & isolation of nanoparticles

Dilution with preheated oil {Heat CL} or Add cross-linking

agent {chemical CL}



PolymerPrecipitation

methods

Solvent extraction method(SEM) Single emulsion



Organic phase,

Solvent, Drug,

Polymer

Aqueous phase,

Distilled water, stabilizer

Sonication, homogenizaion

O/W emulsion

Oil droplet

Solvent evaporation

Nanoparticles obtained

Double Emulsion SEM



Organic phase,

solvent, drug, polymer

Aqueous Phase, Water,

Stabilizer

Sonication, homogenization

W/O emulsion

stablized at 4 C

W/O/W emulsion

Nano particles

Aq phase with stabilizer(PVA)

Solvent evaporation

Solvent Displacement (Nanoprecipitation)



Aq phase Distilled water,

Poloxamer 188

Organic phase, Organic solvent, Polymer, drug

Nano spheres

Aq phaseDistilled Water,

Poloxamer 188

Organic phase,Polar solvent, Oil, Polymer,

Drug

Nano capsules

Magnetic stirring

Salting Out



Org phase. Org solvent,

Drug, Polymer

Aq phase, dist water,

PVA, MgCl2

Mechanical Stirring

O/W emulsion

Nano spheres

Dist Water



Polymerization Based methods

Emulsion Polymerization It may be conventional or reverse, depending

upon nature of continuous phase,Conventional method= Aq phase in ContinuousReverse method= Organic is continuous phase



Monomer is emulsified in non-solvent partially soluble phase with stabilizer, leading to formation of monomer swollen micelles



Polymerization takes place in presence of intiator (chemical/physical), which provides energy to monomer, So that in becomes Free Reactive radical

It collides with the surrounding unnreactive monomers, and initiates the POLYMERIZATiON reaction.

It continues till concentration of monomer/intiator is consumed

Mechanism is micellar polymerization were Swollen monomer micelles act as a site of nucleation & polymerization



As monomer is slightly soluble in surrounding phase, it diffuses from monomer droplets and reach monomer micelles through continuous phase.

Thus polymerization takes places in MICELLES.

Be careful while using Chemical initiator



Flush the Aq medium with nitrogen gas for

1hr to remove completely oxygen

from it.

Interferes the radical polymerization process, Apart from that it forms O radical & We already know HOW HARMFUL

THEY ARE!!!!

Ammonium orPotassium Peroxodisulfate

Dispersion polymerization



Here, monomer instead of being dispersed, is dissolved in the Aq medium, which act as a precipitant for formed polymer.

Nucleation is directly induced in Aq. Monomer solution. So STABILIZER/ SURFACTANT is no needed

Initiation here is achieved by different mechanism, but mostly it is by irradiating solution with high energy radiation (g, UV, strong visible light).

PROCESS GOES AS EMULSION POLYMERIZATION

Interfacial condensation Polymerization



It involves step polymerization of two different monomers, dissolved in two phases respectively, Continuous and Dispersed phase.

Polymerization reaction takes place at the interfaces of two liquids.

Nanometre-sized hollow polymer particles were synthesized by employing interfacial cross-linking reactions as polyaddition and

polycondensation or radical polymerization.



Oil-containing nanocapsules were obtained by the polymerization of monomers at the oil/water interface of a very fine oil-in-water micro- emulsion. The organic

solvent, which was completely miscible with water, served as a monomer vehicle and the interfacial polymerization of the monomer was believed to occur at the

surface of the oil droplets that formed during emulsification

Reverse is the case with preparation of water containing Nanocapusles

Characterization of PNP’s

Particle size and size distribution Surface area, surface chemistry, surface coating and

porosity Hydrophilicity and surface charge density Purity and quality Stability (on shelf and upon administration) Drug release parameters and bioequivalence testing

considerations % Entrapment efficiency % PNP Yield



Size evaluation Done by number of methods with/without Freeze

fracture like Photon correlation spectroscopy,Transmission electron microscopy(TEM)Scanning electron microscopy(SEM)

The spherical shape of the nanocapsules was confirmed by atomic force microscopy

At present, TEM is most successfully used in determining the nanocap structure, polymer envelope and the inner cavity & allowing the wall thickness to be estimated.



Laser Difractometry : For larger particles Freeze fracture has also allowed the visualization of different

possible organizations of lipophilic surfactant, which can form vesicles, micelles, Bilayers, Monolayers,



Surface Charge, Molecular Wt, Structure & Crystallinility Surface Charge: Measuring particle velocity in

electric field Molecule charge: Gel permeation For Structure/crystallinity different thermal

methods are usedDSCDTATGA



Purity, % EE, % Yield

Purity & Quality: Assay of PNP with suitable estimation techniques.

% Entrapement Efficency:

% Yield:



In vitro Drug release

Ideally Franz-diffusion cell is used, but is not appropriate for nano/multiparticulate DDS.

Hence, generally, Cellophane bag filled with the product is used, that is dipped suitable in the beaker filled with proper media, aliquots are taken at regular time intervals.



Applications in some areas of medicine Corticoids release Anticancer therapy Crossing BBB Vaccines and gene therapy Diagnostic Ocular delivery





Products in PipelineCompany Technology API Route of

administrationNovavax, USA Micellar

nanoparticlesTestosterone S.c.

BioAUiance, France Polydsohexylcyanoacrylate)nanoparticles

Doxorubicin i.v.

AmericanBioscience, USA

Albumin-Drugnanoparticles

Paclitaxel i.v.

Wyeth Pharmaceutical, USA

Drug Nanoparticles Rapamycin Oral

BioSante, USA Calcium phospahtenanoparticles

Insulin Oral



Question to Crack GTU

Define nanotechnology and various products prepared by it. Explain application of nanoparticles and nanosuspensions giving examples for their market products. 5M JAN 2011

Briefly introduce the term nanotechnology. Enlist the commonly used polymers into these products. Discuss any one method of preparation of nanoparticle. 6M JUNE 2011

Write about applications of nanoparticulate drug delivery system. 5M JUNE

2011



Explain the terms Nanotechnology and Nanoparticles. Enumerate different parameters and characterization methods for each parameter in context to characterization of Nanoparticulate system.

8M MAY 2012 Nanotechnology and its applications

5M NOV 2012

Give application of nanotechnology in the field of pharmaceutical science 5M DEC 2011



References

Kumari A, Yadav S, Yadav SC, “Biodegradable polymeric nanoparticles based drug delivery systems”,Colloids and Surfaces B: Biointerfaces , elsevier.com, 2010, vol 75 Pg:1–18

Nagavarma BVN, Yadav HKS*, Ayaz A, Vasudha LS, Shivakumar HG. “Different techniques for preparation of polymeric nanoparticles- a review ”, Asian J Pharm Clin Res, Vol 5, Suppl 3, 2012, Pg.16-23

Jain N.K. “Advances in controlled and novel Drug Delivery”, CBS publisher & Distributers, Edition 1st 2001, Pg. 408



Zhang G, Niu A, Peng S, Jiang M, Tu Y, Li M, Wu C, “Formation of Novel Polymeric Nanoparticles”, vol. 34, no. 3, 2001 / accounts of chemical research, pg .249-256

Kreuter J, “Nanoparticles—a historical perspective”, International Journal of Pharmaceutics, vol 331 (2007) elsevier.com,Pg. 1–10

Cismaru L, Popa M,” polymeric nanoparticles with biomedical applications”, Rev. Roum. Chim., vol 55(8) 2010, Pg 433-442



Khar RK and Vyas SP, “Targetted and controlledd drug delivery”

Torchilin p v, “nanoparticulates drug carriers”, imperial college press, london



Thanks for attention,LJIP, Ahmedabad



Education

Polymeric nanoparticles A Novel Approach