Drug Delivery Mechanisms and Encapsulation

Prof. Nedra Karunaratne

Nano material

Nano Intermediate

Nano enabled Product

ProteinsCarbohydrate polymersLipidsSynthetic PolymersPeptides

Nano fibresEmulsions (nano/micro)NanoparticlesLiposomesDendrimers

Encapsulation

Release mechanisms

Encapsulation

Targeted releaseSustained releaseControlled releaseTriggered release- heat, pH, moisture,

etc.

Advantages

•Improved cell penetration•Rapid absorption•Improved bioavailability/ solubility•Reduced toxicity and side effects•Low dose administration•Protection from degradation

Encapsulation: Production of polymeric colloidal particles with a therapeutic agent of interest encapsulated within their polymeric matrix or adsorbed or conjugated onto the surface.

EncapsulationProduction of polymeric colloidal particles with a therapeutic agent of interest encapsulated within their polymeric matrix or adsorbed

or conjugated onto the surface.

Carriers for encapsulation

• Natural polymers- chitosan, alginate, polylactide-co-(PLGL), protein

• Synthetic polymers (biodegradable) – Polyethyleneimine(PEI), N-(2-hydroxypropyl)methacrylamides (HPMA)

• Lipids- phosphatadylcholine,

World Situation

Ref: Int J Nanomedicine. 2014; 9: 4357–4373.

Sri Lankan ScenarioNatural polymers

• Carbohydrate polymers- chitosan, alginate, • Ref Chitosan coated liposomal delivery vehicle for prolonged release of amoxicillin.

M. A. S. K. Menikarachchi, K.A.N.P. Katuvawila, A. Ekanayake, V. Thevanesam, V. Karunaratne and D. N. Karunaratne

(Submitted to JNSF Nov 2014, revised Feb 2015, rerevised Apr 2015 and Sept 2015- still under review)

• Proteins and peptides- whey proteins, albumin, small peptides

• Ref Use of chickpea protein for encapsulation of Folate to enhance nutritional potency and stability. P.G.I.R. Ariyarathna and D.N. Karunaratne. Food and Bioproducts Processing. (2015) 95 , 75 – 82

• Serum stability and Physicochemical Characterization of a Novel Amphipathic peptide C6M1 for siRNA delivery. M. Jafari, W. Xu, R. Pan, C. M. Sweeting, D. N. Karunaratne, and P. Chen. PLOS ONE (2014) 9(5): e97797

Sri Lankan Scenario

• Synthetic polymers -Not known• Nanoparticles – eg. iron oxide nanoparticles

for drug delivery are being researched by two groups in Colombo and Peradeniya.

Sri Lankan ScenarioLipids

• Lipids – liposomes, micelles, emulsions, solid-lipid nanoparticles.

• Ref. Enhanced Liposomal Encapsulation of Ascorbic Acid by the Liquid Crystal b-sitosteryl--D-glucopyranoside. D. M. D. S. Dissanayake, D. N. Karunaratne, and A. D. L. C. Perera. Mol. Cryst. Liq. Cryst, (2015) 613 (1) 94 - 102.

• Optimization of a Liposomal Delivery System for the Highly Antioxidant Methanol Extract of Stem-bark of Schumacheria castaneifolia Vahl. K.M.G.K. Pamunuwa, C. J. Bandara, V.

Karunaratne and D. N. Karunaratne. J. Chem. Pharm. Res. (2015) 7 (4) 1236 - 1245. • Improved skin permeability of dl-α-tocopherol in topical macroemulsions. D.N.

Karunaratne, A.C. Dassanayake, K.M.G.K. Pamunuwa and V. Karunaratne. Int. J. Pharm. Pharmaceutical Sci. (2014) 6 (6) 53 -57.

Innovative Nanomedicine Developments in Switzerland

• InnoMedica, a Swiss nanomedicine company led by Dr. Peter Halbherr, is working towards developing a new nanocarrier platform to transport anti-cancer drugs directly to tumours, thereby avoiding the toxic effect of the drug on healthy cells.

• The platform will deliver existing active agents, initially Doxorubicin, encapsulated in liposomes. The use of Doxorubicin in liposomes is well established and now off patent, being originally released as Doxil.

• InnoMedica’s innovative step is to attach glycans to the surface of the liposomes. Glycans are polymers of carbohydrates, also known as polysaccharides. As an imitation of the detection system of inflammation sites of the immune system, the patented glycan based targeting quickly brings the drug to the cancer site - resulting in a better efficacy, lower dosage and less side effects.

• * Technology for Chitosan coated liposomal delivery system already perfected in Peradeniya-pending journal acceptance

• ** Doxorubicin encapsulated in chitosan nanoparticles, as well as doxorubicin in chitosan-alginate nanoparticles already perfected. Submitted for publication. This work was performed with HETC funding at Peradeniya.

References:1) www.who.int/2) http://www.cancer.org3) http://www.nhs.uk

Way Ahead• Invest in Paharmaceutical manufacturing

companies• Invest in research on nanodelivered drugs- identify

bona fide researchers• Incentives for collaborations between companies

and Universitities• Incubation cells in nanoscience parks.• Animal models for testing drug efficacy is a

neccesity. (tumour models in animals)

• We can do it if the correct atmosphere is provided.

• Thank you

Dendrimers are not encapsulates- but conjugates