**1. Introduction**

Photodynamic therapy (PDT) is an important therapeutic modality used in the treatment of cancer and several non-malignant diseases, including infections and dental treatments [1–5]. It is characterized by the administration of a photosensitizer (PS), a light source to activate it and oxygen molecules (**Figure 1**) [6]. After administration of the photosensitizer, the diseased tissue is irradiated with

#### **Figure 1.**

*PDT mechanism involving the combination of a photosensitizer, a light source and oxygen molecules. After excitation to a higher energy state (1), the photosensitizer may suffer rotovibrational decays to the excited state S1 (2), from which the photosensitizer can suffer energy decay to the fundamental state S0, via fluorescence (3), intersystem crossing (4) or phosphorescence (5).*

visible light, causing the excitation of the PS to a singlet electronic state (S1), which can be deactivated to the fundamental state (S0) through radiative processes (fluorescence or phosphorescence) or non-radioactive (internal conversion, intersystem crossing or vibrational relaxation). Among these processes, intersystem crossing is essential for PDT. It consists of a prohibited transition by spin from the excited singlet electronic state (S1) to the excited triplet state (T1). In this state, the PS can interact with oxygen molecules or other biomolecules that are present in the irradiated tissue generating reactive oxygen species (ROS) that can cause damage to diseased tissues [7, 8]. These ROS can be generated by two mechanisms, [9] involving energy transfer (type II mechanism) or electron transfer (type I mechanism) (**Figure 1**).

The success of the treatment, fundamentally, depends on the photochemical, photobiological and pharmacokinetic properties of the photosensitizer. New porphyrin and phthalocyanine derivatives have been synthesized and encapsulated because their photochemical properties are suitable for PDT [10–12]. In general, hydrophobic photosensitizers tend to form aggregates in aqueous medium, affecting their bioavailability and their ability to generate reactive oxygen species, [13] and consequently, reducing their efficacy in treatment by PDT. In addition, lipophilic molecules hamper the administration of photosensitizer by parenteral via [14]. The nanocarrier systems has proven to be quite effective to solve this problem since they facilitate the administration of the hydrophobic photosensitizer, protect the photosensitizer from aggressive environments and decreasing its aggregation state [15].

Many studies show prominent results with polymeric nanoparticles as carriers of lipophilic photosensitizers due to the benefits associated with their application in PDT for cancer treatment [16–18] such as effectively increase in the amount of PS in the target tissue due to a greater volume/area ratio; prevent the premature release of the photosensitizer, avoiding its accumulation in healthy tissues; maintaining drug concentration at therapeutically appropriate intervals in blood circulation and tissues; greater ability to penetrate the target tissue due to its size; in addition to protecting drugs from liver inactivation and enzymatic degradation [15].

#### *Synergic Influence of Parameters Involved in the Polymeric Nanoparticle Preparation… DOI: http://dx.doi.org/10.5772/intechopen.94176*

Another advantage of polymeric nanoparticles is their biocompatibility and biodegradability, once it is degraded by enzymatic processes that generates nontoxic and biocompatible products, being removed from the body by physiological pathways. An example is the nanoparticle of poly(lactide-co-glycolide) (PLGA), a polymer approved by the Food and Drug Administration (FDA) and that we used in our research [15]. However, it also be reported that the use of nanomaterials in contemporary clinical practice need to be monitored because of the unpredicted effects of the cumulative exposes of non-biodegradable nanoparticle in the human body [19].

Few nanoparticulate formulations are on the shelves of pharmacies due to the lack of knowledge of the combinatorial influence of the parameters used in the preparation of the nanoparticles on the fundamental properties for maximum therapeutic potential, [5] a fact that hampers the scale up process for the production of nanoparticulate formulations. Besides, the poor batch-to batch reproducibility to prepare polymeric nanoparticle, the low solubility of some polymers in water that requires the use of organic solvent to synthesize the nanoparticle, the low glass transition temperature of some polymers that limit the use of them to prepare the nanoparticulate formulation and the high cost of biodegradable polymers are drawback that hamper the development of nanoparticulate pharmaceutic formulation for using in PDT. For these reasons, we have studied the influence of the parameters involved in the preparation of polymeric nanoparticle loaded with several porphyrin and phthalocyanine derivatives (**Figures 2**-**4**) that have different physicochemical properties (**Table 1**).

Given these considerations, we present an overview of the main results obtained by our research group on the influence of several preparation parameters on the final properties of polymeric nanoparticles loaded with photosensitizers for

#### **Figure 2.**

*Molecular structures optimized by Avogadro and MOPAC software for (A) gallium phthalocyanine chlorine (GaPc), (B) indium phthalocyanine chlorine (InPc) and (C) chloro(5,10,15,20-tetraphenylporphyrinato) indium (III) (InTPP).*

#### **Figure 3.**

*Molecular structures optimized by Avogadro and MOPAC software for (A) 5-hexyl-10,20-bi(3-hydroxyphenyl) porphyrin (hex-m-bisHPP), (B) 5-hexyl-10,15,20-tri(3-hydroxyphenyl)porphyrin (hex-m-trisHPP) and (C) 5,10,15,20-tetra(3-hydroxyphenyl)porphyrin (m-THPP).*

#### **Figure 4.**

*Molecular structures optimized by Avogadro and MOPAC software for 1,4-(tetrakis[4-(benzyloxy)phenoxy] phthalocyaninato) indium(III) chloride (InTBPPc).*

application in PDT, besides regarding the effect of encapsulation in reducing the photobleaching process of photosensitizer and on the efficiency of nanoparticles containing photosensitive compounds in reducing the viability of cancer cells or in biomolecules photooxidation.


**Table 1.**

*Physicochemical properties of the studied photosensitizers.*

*Synergic Influence of Parameters Involved in the Polymeric Nanoparticle Preparation… DOI: http://dx.doi.org/10.5772/intechopen.94176*
